Sialic acid-binding lectin-modified fructose-coated nanoparticles: a promising targeted therapeutic synthetic for breast cancers

Abstract Background: Sialic acid-binding lectin (cSBL) specifically kills tumor cells rather than healthy cells. Glycopolymer-coated nanoparticles are selectively ingested by tumor cells because they can interact with the enriched carbohydrate receptors located on the surface of tumor cells. In this context, we synthesized cSBL-modified fructose-coated nanoparticles (LMFN) and cSBL-modified glucose-coated nanoparticles (LMGN) to investigate their anticancer activity in various molecular subtypes of breast cancer cell lines. Methods: The syntheses of fructose-coated nanoparticles and glucose-coated nanoparticles were based on the chemicals of 1,2:4,5-di- O -isopropylidene- β -d-fructopyranose and 1,2:4,5-di- O -isopropylidene- β -d-glucopyranose, respectively. The carbodiimide-based method was employed to synthesize LMFN and LMGN. The antitumor mechanism was explored by cell cycle analysis with flowcytometry and the antitumor activity was assessed by cytotoxicity assay and multiple drug effects analysis. Results: The cytotoxicity assay showed that LMFN had robust antitumor activity against all breast cancer phenotype cell lines whereas LMGN was rarely efficacious to against human epidermal growth factor receptor 2-positive/overexpression (HER2+/overexpression) breast cancer cells. The intrinsic reason for these findings was that the overexpression of fructose transporter, GLUT5, was observed in all breast cancer subtype cell lines but only a paucity of glucose transporter, GLUT1, was expressed in HER2+/overexpression breast cancer cell lines that dampened the uptake of LMGN to these cells. The cell cycle analysis indicated that the anticancer activity of LMFN was achieved by arresting cell cycle in S phase. The multiple drug effects analysis suggested the synergistic effect in the combinations of LMFN and tamoxifen to kill estrogen receptor+ breast cancer cells and LMFN and trastuzumab to kill HER2+/overexpressed breast cancer cells. Conclusion: Our work pinpoints that LMFN may be a new-onset selection for molecularly targeted therapy of breast cancers and paves the way for establishing its clinical application in the future.

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Sialic acid-binding lectin-modified fructose-coated nanoparticles: a promising targeted therapeutic synthetic for breast cancers

10.21203/rs.2.23056/v2 ◽

2020 ◽

Author(s):

Lin He ◽

Biyuan Zhang ◽

Yuhua Song ◽

Haiji Wang

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Tumor Cells ◽

Cell Lines ◽

Drug Effects ◽

Multiple Drug ◽

Her2 Overexpression ◽

Breast Cancers ◽

Coated Nanoparticles ◽

Sialic Acid Binding

Abstract Background: Sialic acid-binding lectin (cSBL) specifically kills tumor cells rather than healthy cells. Glycopolymer-coated nanoparticles are selectively ingested by tumor cells because they can interact with the enriched carbohydrate receptors located on the surface of tumor cells. In this context, we synthesized cSBL-modified fructose-coated nanoparticles (LMFN) and cSBL-modified glucose-coated nanoparticles (LMGN) to investigate their anticancer activity in various molecular subtypes of breast cancer cell lines.Methods: The syntheses of fructose-coated nanoparticles and glucose-coated nanoparticles were based on the chemicals of 1,2:4,5-di-O-isopropylidene-β-d-fructopyranose and 1,2:4,5-di-O-isopropylidene-β-d-glucopyranose, respectively. The carbodiimide-based method was employed to synthesize LMFN and LMGN. The antitumor mechanism was explored by cell cycle analysis with flowcytometry and the antitumor activity was assessed by cytotoxicity assay and multiple drug effects analysis.Results: The cytotoxicity assay showed that LMFN had robust antitumor activity against all breast cancer phenotype cell lines whereas LMGN was rarely efficacious to against human epidermal growth factor receptor 2-positive/overexpression (HER2+/overexpression) breast cancer cells. The intrinsic reason for these findings was that the overexpression of fructose transporter, GLUT5, was observed in all breast cancer subtype cell lines but only a paucity of glucose transporter, GLUT1, was expressed in HER2+/overexpression breast cancer cell lines that dampened the uptake of LMGN to these cells. The cell cycle analysis indicated that the anticancer activity of LMFN was achieved by arresting cell cycle in S phase. The multiple drug effects analysis suggested the synergistic effect in the combinations of LMFN and tamoxifen to kill estrogen receptor+ breast cancer cells and LMFN and trastuzumab to kill HER2+/overexpressed breast cancer cells.Conclusion: Our work pinpoints that LMFN may be a new-onset selection for molecularly targeted therapy of breast cancers and paves the way for establishing its clinical application in the future.

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Periostin gene expression in neu-positive breast cancer cells is regulated by a FGFR signaling cross talk with TGFβ/PI3K/AKT pathways

Breast Cancer Research ◽

10.1186/s13058-021-01487-8 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Cédrik Labrèche ◽

David P. Cook ◽

John Abou-Hamad ◽

Julia Pascoal ◽

Benjamin R. Pryce ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Cells ◽

Tumor Cells ◽

Cell Lines ◽

Breast Cancer Cells ◽

Breast Cancer Cell Lines ◽

Matricellular Protein ◽

Stromal Compartment ◽

Primary Tumors

Abstract Background Breast cancer is a highly heterogeneous disease with multiple drivers and complex regulatory networks. Periostin (Postn) is a matricellular protein involved in a plethora of cancer types and other diseases. Postn has been shown to be involved in various processes of tumor development, such as angiogenesis, invasion, cell survival and metastasis. The expression of Postn in breast cancer cells has been correlated with a more aggressive phenotype. Despite extensive research, it remains unclear how epithelial cancer cells regulate Postn expression. Methods Using murine tumor models and human TMAs, we have assessed the proportion of tumor samples that have acquired Postn expression in tumor cells. Using biochemical approaches and tumor cell lines derived from Neu+ murine primary tumors, we have identified major regulators of Postn gene expression in breast cancer cell lines. Results Here, we show that, while the stromal compartment typically always expresses Postn, about 50% of breast tumors acquire Postn expression in the epithelial tumor cells. Furthermore, using an in vitro model, we show a cross-regulation between FGFR, TGFβ and PI3K/AKT pathways to regulate Postn expression. In HER2-positive murine breast cancer cells, we found that basic FGF can repress Postn expression through a PKC-dependent pathway, while TGFβ can induce Postn expression in a SMAD-independent manner. Postn induction following the removal of the FGF-suppressive signal is dependent on PI3K/AKT signaling. Conclusion Overall, these results reveal a novel regulatory mechanism and shed light on how breast tumor cells acquire Postn expression. This complex regulation is likely to be cell type and cancer specific as well as have important therapeutic implications.

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Interaction of Tumor Cells with the Hematopoietic Stem and Progenitor Cell Niche

Blood ◽

10.1182/blood.v124.21.5139.5139 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5139-5139 ◽

Cited By ~ 1

Author(s):

Abhishek Dhawan ◽

Jens Friedrichs ◽

Laura Bray ◽

Lorenz C. Hofbauer ◽

Manja Wobus ◽

...

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Cancer Cells ◽

Tumor Cells ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Breast Cancer Cell Lines ◽

Mcf 7

Abstract Introduction The bone marrow microenvironment regulates the self-renewal and differentiation of hematopoietic stem and progenitor cells (HSPCs), through a network dependent on cell-cell interaction. This interaction is mediated by morphogens, the extracellular matrix and cell adhesion molecules expressed and secreted by various cell types in the HSPC niche. Mesenchymal stromal cells (MSCs), as the major cellular component, maintain the stemness properties of the niche. The microenvironment thus becomes conducive for HSPCs to remain quiescent, thereby enabling long term self-renewal. Therefore, the safe haven in the bone marrow microenvironment and its constituent cell types can be targeted during tumorigenesis, thus making the niche neoplastic. Dissemination of breast cancer cells into the bone marrow has been described even in the early stages of the disease. The present study focuses on the influence of breast carcinomas on the genetic and functional profile of mesenchymal and hematopoietic progenitor cells of the bone marrow niche. Methods In vitro coculture models of breast cancer cell lines- MDA-MB231, MCF-7 and primary MSCs derived from the bone marrow of healthy donors were used in the study. Atomic- force microscopy based single-cell force spectroscopy (AFM-SCFS) and fluorescence based assays were used for cell adhesion experiments. Hydrogel based culture systems were used for 3-dimensional cocultures of breast cancer cells and MSCs. Hypoxic and normoxic culture conditions (0.5% and 20% oxygen respectively) were used for the experiments. Results The breast cancer cell lines caused a significant reduction in HSPC adhesion to MSCs (88% by MDA-MB 231 cells; p<0.005 and 73% by MCF-7 cells; p<0.005). AFM-SCFS studies also indicated a higher binding force between breast cancer cells and MSCs, as compared to HSPCs (MDA-MB231 cells-0.13nN, MCF-7 cells-0.074nN and HSPCs-0.05nN). MDA-MB231and MCF-7 cells express Intercellular adhesion molecule-1(ICAM-1), which has been shown to promote breast cancer metastasis (Hanlon et al, 2002; Rosette et al, 2005; Schröder C. et al, 2011). There was a significant difference in reduction of HSPC adhesion towards MSCs by ICAM-1 knockdown (ICAM-1 KD) tumor cells as compared to MDA-MB231 cells (84.83% by MDA-MB231 cells versus 28.11% by ICAM-1KD tumor cells, p<0.001). AFM-SCFS studies also showed a reduced binding force between ICAM-1 KD tumor cells and MSCs as compared to MDA-MB231cells (MDA-MB231 cells-0.14nN versus ICAM-1-KD tumor cells-0.05nN, p value<0.001). ICAM-1 KD studies thus showed that reduction in HSPC adhesion to MSCs by breast cancer cells was mediated through ICAM-1 signaling. A cytokine array was performed to investigate if breast cancer cell lines affect the cytokine profile of MSCs. The array showed altered expression of growth factors- Basic fibroblast growth factor (bFGF) and Platelet derived growth factor–beta (PDGF-BB) (2.2 fold upregulation and 0.5 fold downregulation in breast cancer cells- MSC cocultures respectively). Based on the array, a bFGF-mediated increase in the proliferation of MSCs and breast cancer cells in coculture was observed. The bFGF upregulation also caused an increased migration of MDA-MB231 cells towards MSCs in a transwell migration assay. An upregulation in the phosphorylation status of Akt was observed in breast cancer cells – MSC cocultures, as a downstream effect of upregulated bFGF levels. The bFGF-mediated increase in the proliferation of breast cancer cells and MSCs in coculture was shown to be dependent on the activation of PI3K-Akt pathway. The bFGF- mediated increase in the migration of MDA-MB231 cells towards MSCs was also inhibited upon addition of the PI3K blocker. Interestingly, the breast cancer cells caused a reduction in osteoblastic differentiation of MSCs by downregulation of PDGF-BB. Studies with 3-dimensional cocultures of breast cancer cells and MSCs also showed a reduction in osteoblastic differentiation of MSCs. Furthermore, long-term cocultures of breast cancer cells, HSPCs and MSCs showed reduced support for primitive HSPCs in the neoplastic niche. Conclusions These findings indicate a perturbed HSPC niche upon tumor invasion. The possible role of altered cytokine expression, consecutive downstream signaling in niche activation and bone turnover will be further studied using in vitro and in vivo approaches to recapitulate tumor micrometastases to the HSPC niche. Disclosures No relevant conflicts of interest to declare.

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Effect of new anti-neoplastic agent, MK615, from Japanese apricot, ume, on growth of breast cancer cells in vitro

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.11105 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 11105-11105

Author(s):

A. Nakagawa ◽

T. Sawada ◽

T. Okada ◽

T. Ohsawa ◽

M. Adachi ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Growth Inhibition ◽

Cancer Cells ◽

Cell Lines ◽

Breast Cancer Cells ◽

Breast Cancer Cell Lines ◽

Dependent Manner ◽

Japanese Apricot

11105 Background: MK615 is an extract mixture from Japanese apricot, UME. In this study, the anti-neoplastic effects of MK615 against breast cancer cells were investigated. Methods: Two breast cancer cell lines, MDA-MB-468 (MDA) and MCF7, were cultured with (600, 300, 150 μg/ml) or without MK615. After 72 hours of incubation, growth inhibition was evaluated by MTT assay, and the mechanism of the anti-neoplastic effect of MK615 was evaluated by cell cycle- and apoptosis assay. Results: MK615 inhibited the growth of MDA and MCF7 in a dose-dependent manner. The percentage growth inhibition of MDA at dosages of 600, 300, and 150 μg/ml was 59.2%, 52.4%, and 23.3%, respectively, and that for MCF7 was 83.5%, 52.7%, and 16.6%, respectively. Cell cycle analysis showed that MK615 increased the proportion of cells in G2-M phase in both MDA (7.8% to 11.7%) and MCF7 (8.1% to 18.7%), and finally both cell lines became apoptotic. The proportion of apoptotic cells increased with incubation time. Conclusions: MK615 effectively inhibits the growth of breast cancer cells in vitro, possibly by cell cycle modification and apoptosis induction. No significant financial relationships to disclose.

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Despite Blocking Doxorubicin-Induced Vascular Damage, Quercetin Ameliorates Its Antibreast Cancer Activity

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/8157640 ◽

2020 ◽

Vol 2020 ◽

pp. 1-14

Author(s):

Hanan A. Henidi ◽

Fahad A. Al-Abbasi ◽

Mohamed A. El-Moselhy ◽

Hany M. El-Bassossy ◽

Ahmed M. Al-Abd

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Cell Lines ◽

Breast Cancer Cells ◽

Breast Cancer Cell Lines ◽

Ros Generation ◽

Atpase Subunit ◽

T47d Cells ◽

Mcf 7

Quercetin is a naturally occurring flavonol present in many foods. Doxorubicin is an effective anticancer agent despite its dose-limiting cardiovascular toxicity. Herein, we investigated the potential protective effects of quercetin against doxorubicin-induced vascular toxicity and its effect on the therapeutic cytotoxic profile of doxorubicin in breast cancer cell lines. The incubation of isolated aortic rings with doxorubicin produced concentration-dependent exaggeration of vasoconstriction responses to phenylephrine but impaired vasodilation responses to acetylcholine. Coincubation with quercetin completely blocked the exaggerated vasoconstriction responses and the impaired vasodilation. In addition, doxorubicin incubation increased reactive oxygen species generation from the isolated aorta, while coincubation with quercetin inhibited ROS generation back to normal values. On the other hand, quercetin in combination with doxorubicin, doubled the IC50 of doxorubicin alone in MCF-7 cells from 0.4±0.03 to 0.8±0.06 μM. To a lesser extent, the IC50 of doxorubicin did not change after combination with quercetin in MDA-MB-231 cells. These findings indicate a significant antagonistic interaction between quercetin and doxorubicin in the aforementioned cell lines. Only in T47D cells, quercetin combination with doxorubicin was an additive interaction (CI−value=1.17). Yet, quercetin significantly impaired the immediate phase of intracellular ROS generation by doxorubicin within breast cancer cells from 125.2±3.6% to 102.5±3.9% of control cells. Using annexin-V/FITC staining technique, the quercetin/doxorubicin combination showed a significantly lower percent of apoptotic cells compared to doxorubicin alone treated cells. Cell cycle distribution in breast cancer cells was performed using DNA content flowcytometry after propidium iodide staining. Quercetin induced significant accumulation of cells in the S phase as well as in the G2/M phase within both MCF-7 and MDA-MB-231 cell lines and interfered with doxorubicin-induced cell cycle effects. Interestingly, quercetin was found to inhibit the P-glycoprotein ATPase subunit with a consequent enhanced intracellular concentration of doxorubicin in MDA-MB-231 and T47D cells. In conclusion, quercetin, despite its potent vascular protective activity against doxorubicin, was found to influence doxorubicin-induced antibreast cancer effects via pharmacodynamic as well as cellular pharmacokinetic aspects.

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Orai2 Modulates Store-Operated Ca2+ Entry and Cell Cycle Progression in Breast Cancer Cells

Cancers ◽

10.3390/cancers14010114 ◽

2021 ◽

Vol 14 (1) ◽

pp. 114

Author(s):

Jose Sanchez-Collado ◽

Jose J. Lopez ◽

Carlos Cantonero ◽

Isaac Jardin ◽

Sergio Regodón ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Apoptosis Resistance

Breast cancer is a heterogeneous disease from the histological and molecular expression point of view, and this heterogeneity determines cancer aggressiveness. Store-operated Ca2+ entry (SOCE), a major mechanism for Ca2+ entry in non-excitable cells, is significantly remodeled in cancer cells and plays an important role in the development and support of different cancer hallmarks. The store-operated CRAC (Ca2+ release-activated Ca2+) channels are predominantly comprised of Orai1 but the participation of Orai2 and Orai3 subunits has been reported to modulate the magnitude of Ca2+ responses. Here we provide evidence for a heterogeneous expression of Orai2 among different breast cancer cell lines. In the HER2 and triple negative breast cancer cell lines SKBR3 and BT20, respectively, where the expression of Orai2 was greater, Orai2 modulates the magnitude of SOCE and sustain Ca2+ oscillations in response to carbachol. Interestingly, in these cells Orai2 modulates the activation of NFAT1 and NFAT4 in response to high and low agonist concentrations. Finally, we have found that, in cells with high Orai2 expression, Orai2 knockdown leads to cell cycle arrest at the G0-G1 phase and decreases apoptosis resistance upon cisplatin treatment. Altogether, these findings indicate that, in breast cancer cells with a high Orai2 expression, Orai2 plays a relevant functional role in agonist-evoked Ca2+ signals, cell proliferation and apoptosis resistance.

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Antiplatelet Therapy Combined with Anastrozole Induces Features of Partial EMT in Breast Cancer Cells and Fails to Mitigate Breast-Cancer Induced Hypercoagulation

International Journal of Molecular Sciences ◽

10.3390/ijms22084153 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4153

Author(s):

Kutlwano R. Xulu ◽

Tanya N. Augustine

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Patients ◽

Antiplatelet Therapy ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines

Thromboembolic complications are a leading cause of morbidity and mortality in cancer patients. Cancer patients often present with an increased risk for thrombosis including hypercoagulation, so the application of antiplatelet strategies to oncology warrants further investigation. This study investigated the effects of anastrozole and antiplatelet therapy (aspirin/clopidogrel cocktail or atopaxar) treatment on the tumour responses of luminal phenotype breast cancer cells and induced hypercoagulation. Ethical clearance was obtained (M150263). Blood was co-cultured with breast cancer cell lines (MCF7 and T47D) pre-treated with anastrozole and/or antiplatelet drugs for 24 h. Hypercoagulation was indicated by thrombin production and platelet activation (morphological and molecular). Gene expression associated with the epithelial-to-mesenchymal transition (EMT) was assessed in breast cancer cells, and secreted cytokines associated with tumour progression were evaluated. Data were analysed with the PAST3 software. Our findings showed that antiplatelet therapies (aspirin/clopidogrel cocktail and atopaxar) combined with anastrozole failed to prevent hypercoagulation and induced evidence of a partial EMT. Differences in tumour responses that modulate tumour aggression were noted between breast cancer cell lines, and this may be an important consideration in the clinical management of subphenotypes of luminal phenotype breast cancer. Further investigation is needed before this treatment modality (combined hormone and antiplatelet therapy) can be considered for managing tumour associated-thromboembolic disorder.

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Super Magnetic Niosomal Nanocarrier as a New Approach for Treatment of Breast Cancer: A Case Study on SK-BR-3 and MDA-MB-231 Cell Lines

International Journal of Molecular Sciences ◽

10.3390/ijms22157948 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7948

Author(s):

Elham Jamshidifar ◽

Faten Eshrati Yeganeh ◽

Mona Shayan ◽

Mohammad Tavakkoli Yaraki ◽

Mahsa Bourbour ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Cellular Uptake ◽

Targeted Delivery ◽

Breast Cancer Cells ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Silica Layer

In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe2O4 core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe2O4@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe2O4@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents.

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Highly expressed SLCO1B3 inhibits the occurrence and development of breast cancer and can be used as a clinical indicator of prognosis

Scientific Reports ◽

10.1038/s41598-020-80152-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tiantian Tang ◽

Guiying Wang ◽

Sihua Liu ◽

Zhaoxue Zhang ◽

Chen Liu ◽

...

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Migration And Invasion ◽

Breast Cancer Cell Lines

AbstractThe role of organic anion transporting polypeptide 1B3 (SLCO1B3) in breast cancer is still controversial. The clinical immunohistochemical results showed that a greater proportion of patients with negative lymph nodes, AJCC stage I, and histological grade 1 (P < 0.05) was positively correlated with stronger expression of SLCO1B3, and DFS and OS were also increased significantly in these patients (P = 0.041, P = 0.001). Further subgroup analysis showed that DFS and OS were significantly enhanced with the increased expression of SLCO1B3 in the ER positive subgroup. The cellular function assay showed that the ability of cell proliferation, migration and invasion was significantly enhanced after knockdown of SLCO1B3 expression in breast cancer cell lines. In contrast, the ability of cell proliferation, migration and invasion was significantly reduced after overexpress the SLCO1B3 in breast cancer cell lines (P < 0.05). Overexpression or knockdown of SLCO1B3 had no effect on the apoptotic ability of breast cancer cells. High level of SLCO1B3 expression can inhibit the proliferation, invasion and migration of breast cancer cells, leading to better prognosis of patients. The role of SLCO1B3 in breast cancer may be related to estrogen. SLCO1B3 will become a potential biomarker for breast cancer diagnosis and prognosis assessment.

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MicroRNA in combination with HER2-targeting drugs reduces breast cancer cell viability in vitro

Scientific Reports ◽

10.1038/s41598-021-90385-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lisa Svartdal Normann ◽

Miriam Ragle Aure ◽

Suvi-Katri Leivonen ◽

Mads Haugland Haugen ◽

Vesa Hongisto ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Breast Cancer Cells ◽

Targeted Treatment ◽

Breast Cancer Cell Lines ◽

Altered Expression ◽

Her2 Breast Cancer

AbstractHER2-positive (HER2 +) breast cancer patients that do not respond to targeted treatment have a poor prognosis. The effects of targeted treatment on endogenous microRNA (miRNA) expression levels are unclear. We report that responsive HER2 + breast cancer cell lines had a higher number of miRNAs with altered expression after treatment with trastuzumab and lapatinib compared to poorly responsive cell lines. To evaluate whether miRNAs can sensitize HER2 + cells to treatment, we performed a high-throughput screen of 1626 miRNA mimics and inhibitors in combination with trastuzumab and lapatinib in HER2 + breast cancer cells. We identified eight miRNA mimics sensitizing cells to targeted treatment, miR-101-5p, mir-518a-5p, miR-19b-2-5p, miR-1237-3p, miR-29a-3p, miR-29c-3p, miR-106a-5p, and miR-744-3p. A higher expression of miR-101-5p predicted better prognosis in patients with HER2 + breast cancer (OS: p = 0.039; BCSS: p = 0.012), supporting the tumor-suppressing role of this miRNA. In conclusion, we have identified miRNAs that sensitize HER2 + breast cancer cells to targeted therapy. This indicates the potential of combining targeted drugs with miRNAs to improve current treatments for HER2 + breast cancers.

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