scholarly journals The Synergistic Effects of SHR6390 Combined With Pyrotinib on HER2+/HR+ Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Yukun Wang ◽  
Xiang Yuan ◽  
Jing Li ◽  
Zhiwei Liu ◽  
Xinyang Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Molecular Mechanisms ◽  
Xenograft Model ◽  
Cancer Cell Lines ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

HER2+/HR+ breast cancer is a special molecular type of breast cancer. Existing treatment methods are prone to resistance; “precision treatment” is necessary. Pyrotinib is a pan-her kinase inhibitor that can be used in HER2-positive tumors, while SHR6390 is a CDK4/6 inhibitor that can inhibit ER+ breast cancer cell cycle progression and cancer cell proliferation. In cancer cells, HER2 and CDK4/6 signaling pathways could be nonredundant; co-inhibition of both pathways by combination of SHR6390 and pyrotinib may have synergistic anticancer activity on HER2+/HR+ breast cancer. In this study, we determined the synergy of the two-drug combination and underlying molecular mechanisms. We showed that the combination of SHR6390 and pyrotinib synergistically inhibited the proliferation, migration, and invasion of HER2+/HR+ breast cancer cells in vitro. The combination of two drugs induced G1/S phase arrest and apoptosis in HER2+/HR+ breast cancer cell lines. The combination of two drugs prolonged the time to tumor recurrence in the xenograft model system. By second-generation RNA sequencing technology and enrichment analysis of the pyrotinib-resistant cell line, we found that FOXM1 was associated with induced resistance to HER2-targeted therapy. In HER2+/HR+ breast cancer cell lines, the combination of the two drugs could further reduce FOXM1 phosphorylation, thereby enhancing the antitumor effect to a certain extent. These findings suggest that SHR6390 combination with pyrotinib suppresses the proliferation, migration, and invasion of HER2+/HR+ breast cancers through regulation of FOXM1.

scholarly journals LOC550643, a Long Non-coding RNA, Acts as Novel Oncogene in Regulating Breast Cancer Growth and Metastasis

2021 ◽  
Vol 9 ◽  
Author(s):  
Kuo-Wang Tsai ◽  
Kian-Hwee Chong ◽  
Chao-Hsu Li ◽  
Ya-Ting Tu ◽  
Yi-Ru Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Metastatic Breast ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines

Metastatic disease is responsible for over 90% of death in patients with breast cancer. Therefore, identifying the molecular mechanisms that regulate metastasis and developing useful therapies are crucial tasks. Long non-coding RNAs (lncRNAs), which are non-coding transcripts with >200 nucleotides, have recently been identified as critical molecules for monitoring cancer progression. This study examined the novel lncRNAs involved in the regulation of tumor progression in breast cancer. This study identified 73 metastasis-related lncRNA candidates from comparison of paired isogenic high and low human metastatic breast cancer cell lines, and their expression levels were verified in clinical tumor samples by using The Cancer Genome Atlas. Among the cell lines, a novel lncRNA, LOC550643, was highly expressed in breast cancer cells. Furthermore, the high expression of LOC550643 was significantly correlated with the poor prognosis of breast cancer patients, especially those with triple-negative breast cancer. Knockdown of LOC550643 inhibited cell proliferation of breast cancer cells by blocking cell cycle progression at S phase. LOC550643 promoted important in vitro metastatic traits such as cell migration and invasion. Furthermore, LOC550643 could inhibit miR-125b-2-3p expression to promote breast cancer cell growth and invasiveness. In addition, by using a xenograft mouse model, we demonstrated that depletion of LOC550643 suppressed the lung metastatic potential of breast cancer cells. Overall, our study shows that LOC550643 plays an important role in breast cancer cell metastasis and growth, and LOC550643 could be a potential diagnosis biomarker and therapeutic target for breast cancer.

Small Molecular Leads Differentially Active Against HER2 Positive and Triple Negative Breast Cancer Cell Lines

2019 ◽  
Vol 15 (7) ◽  
pp. 738-742 ◽  
Author(s):  
Adnan Badran ◽  
Atia-tul-Wahab ◽  
Sharmeen Fayyaz ◽  
Elias Baydoun ◽  
Muhammad Iqbal Choudhary
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Triple Negative ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Cancer Type

Background:Breast cancer is the most prevalent cancer type in women globally. It is characterized by distinct subtypes depending on different gene expression patterns. Oncogene HER2 is expressed on the surface of cell and is responsible for cell growth regulation. Increase in HER2 receptor protein due to gene amplification, results in aggressive growth, and high metastasis in cancer cells.Methods:The current study evaluates and compares the anti-breast cancer effect of commercially available compounds against HER2 overexpressing BT-474, and triple negative MDA-MB-231 breast cancer cell lines.Results:Preliminary in vitro cell viability assays on these cell lines identified 6 lead molecules active against breast cancer. Convallatoxin (4), a steroidal lactone glycoside, showed the most potent activity with IC50 values of 0.63 ± 0.56, and 0.69 ± 0.59 µM against BT-474 and MDA-MB-231, respectively, whereas 4-[4-(Trifluoromethyl)-phenoxy] phenol (3) a phenol derivative, and Reserpine (5) an indole alkaloid selectively inhibited the growth of BT-474, and MDA-MB-231 breast cancer cells, respectively.Conclusion:These results exhibited the potential of small molecules in the treatment of HER2 amplified and triple negative breast cancers in vitro.

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

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.

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

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.

The α2δ1 subunit of the voltage-gated calcium channel as a potential candidate for breast cancer tumor initial cells biomarker

2021 ◽  
pp. 1-11
Author(s):  
Meng Li ◽  
Wenmin Zhang ◽  
Xiaodan Yang ◽  
Guo An ◽  
Wei Zhao
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Self Renewal

BACKGROUND: The voltage-gated calcium channel subunit alpha 2 delta 1 (α2δ1) is a functional tumor initial cells (TICs) marker for some solid cancer cells. This study aimed to investigate whether α2δ1 can be used as a potential TIC marker for breast cancer cells. METHODS: α2δ1+ and α2δ1- cells were identified and sorted from the breast cancer cell lines MDA-MB-231, MDA-MB-435s and ZR-75-1 by Immunofluorescence (IF) and Fluorescent-activated cell sorting (FACS) analyses. Spheroid formation in vitro and tumorigenesis in NOD/SCID mice were assessed to determine the self-renewal and serial transplantation abilities of these cells. Using a lentivirus infection system for α2δ1 in breast cancer cell lines, we determined the mRNA levels of stemnessassociated genes by quality real-time PCR (qRT-PCR). Boyden chamber and wounding assays were further performed to detect the migration of α2δ1 overexpression cells. Bioinformatics explored the relationship of molecular classification of breast cancer and drug resistance. RESULTS: α2δ1 presents on the cytomembrane of breast cancer cells, with a positive rate of 1.5–3%. The α2δ1+ cells in breast cancer cell lines have a stronger self-renewal ability and tumor initiating properties in vitro and in vivo. Overexpressing α2δ1 successfully enhanced the sphere-forming efficiency, and upregulated the expression of stemness-associated genes, and increased cell migration. However, seldom significant was available between estrogen receptor +/- (ER+/-), progesterone receptor (PR+/-), and Her2+/-. CONCLUSIONS: Breast cancer cells positive for the α2δ1 charactered tumor initiation, and α2δ1 is a potential TIC marker for breast cancer that further promotes the migration.

scholarly journals TRPC6 Channels Are Required for Proliferation, Migration and Invasion of Breast Cancer Cell Lines by Modulation of Orai1 and Orai3 Surface Exposure

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 331 ◽  
Author(s):  
Isaac Jardin ◽  
Raquel Diez-Bello ◽  
Jose Lopez ◽  
Pedro Redondo ◽  
Ginés Salido ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Transient Receptor Potential Channels ◽  
Brdu Incorporation ◽  
Migration And Invasion ◽  
Breast Cancer Cell Lines ◽  
Mcf10a Cell

Transient receptor potential channels convey signaling information from a number of stimuli to a wide variety of cellular functions, mainly by inducing changes in cytosolic Ca2+ concentration. Different members of the TRPC, TRPM and TRPV subfamilies have been reported to play a role in tumorigenesis. Here we show that the estrogen receptor positive and triple negative breast cancer cell lines, MCF7 and MDA-MB-231, respectively, exhibit enhanced expression of the TRPC6 channel as compared to the non-tumoral MCF10A cell line. In vitro TRPC6 knockdown using shRNA impaired MCF7 and MDA-MB-231 cell proliferation, migration and invasion detected by BrdU incorporation, wound healing and Boyden chamber assays, respectively. Using RNAi-mediated TRPC6 silencing as well as overexpression of the pore-dead dominant-negative TRPC6 mutant we have found that TRPC6 plays a relevant role in the activation of store-operated Ca2+ entry in the breast cancer cell lines but not in non-tumoral breast cells. Finally, we have found that TRPC6 interacts with Orai1 and Orai3 in MCF7 and MDA-MB-231 cells and is required for the translocation of Orai1 and Orai3 to the plasma membrane in MDA-MB-231 and MCF7 cells, respectively, upon Ca2+ store depletion. These findings introduce a novel mechanism for the modulation of Ca2+ influx and the development of different cancer hallmarks in breast cancer cells.

scholarly journals Molecular Simulations Identify Target Receptor Kinases Bound by Astaxanthin to Induce Breast Cancer Cell Apoptosis

2020 ◽  
pp. 72-82
Author(s):  
Mossa Gardaneh ◽  
Zahra Nayeri ◽  
Parvin Akbari ◽  
Mahsa Gardaneh ◽  
Hasan Tahermansouri
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Combination Therapy ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Molecular Mechanisms ◽  
Cancer Cell Lines ◽  
Cancer Drug ◽  
Breast Cancer Cell Lines

Background: We investigated molecular mechanisms behind astaxanthinmediated induction of apoptosis in breast cancer cell lines toward combination therapy against cancer drug resistance. Methods: Breast cancer cell lines were treated with serial concentrations of astaxanthin to determine its IC50. We used drug-design software to predict interactions between astaxanthin and receptor tyrosine kinases or other key gene products involved in intracellular signaling pathways. Changes in gene expression were examined using RT-PCR. The effect of astaxanthin-nanocarbons combinations on cancer cells was also evaluated. Results: Astaxanthin induced cell death in all three breast cancer cell lines was examined so that its IC50 in two HER2-amplifying lines SKBR3 and BT-474 stood, respectively, at 36 and 37 ?M; however, this figure for MCF-7 was significantly lowered to 23 ?M (P<0.05). Astaxanthin-treated SKBR3 cells showed apoptotic death upon co-staining. Our in silico examinations showed that some growth-promoting molecules are strongly bound by astaxanthin via their specific amino acid residues with their binding energy standing below -6 KCa/Mol. Next, astaxanthin was combined with either graphene oxide or carboxylated multi-walled carbon nanotube, with the latter affecting SKBR cell survival more extensively than the former (P<0.05). Finally, astaxanthin coinduced tumor suppressors p53 and PTEN but downregulated the expression of growth-inducing genes in treated cells. Conclusion: These findings indicate astaxanthin carries' multitarget antitumorigenic capacities and introduce the compound as a suitable candidate for combination therapy regimens against cancer growth and drug resistance. Development of animal models to elucidate interactions between the compound and tumor microenvironment could be a major step forward towards the inclusion of astaxanthin in cancer therapy trials.

Solanum nigrum Anticancer Effect Through Epigenetic Modulations in Breast Cancer Cell Lines

2020 ◽  
Vol 16 (2) ◽  
pp. 121-126
Author(s):  
Atefeh Shirkavand ◽  
Zahra N. Boroujeni ◽  
Seyed A. Aleyasin
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Methylation Status ◽  
Cancer Cell Lines ◽  
Solanum Nigrum ◽  
Breast Cancer Cell Lines

Background: DNA methylation plays an important role in the regulation of gene expression in mammalian cells and often occurs at CpG islands in the genome. It is more reversible than genetic variations and has therefore attracted much attention for the treatment of many diseases, especially cancer. In the present study, we investigated the effect of Solanum nigrum Extract (SNE) on the methylation status of the VIM and CXCR4 genes in breast cancer cell lines. Methods: The Trypan blue assay was used to study the effect of SNE at various concentrations of 0, 0.1, 1.5, 2.5, 3.5 and 5 mg/ml for 48 h on the survival of three human breast cancer cell lines MCF7, MDA-MB-468, MDA-MB-231. Methylation status of VIM and CXCR4 genes in breast cancer cell lines was assessed by Methylation-Specific PCR (MSP) method. Also, methylation changes of VIM and CXCR4 genes in breast cancer cell lines after treatment with 0.1 mg/ml of SNE for 6 days were analyzed by MSP method. To confirm the effect of SNE on methylation of VIM and CXCR4 genes, Real-Time PCR was performed. Results: The Trypan blue assay results indicated that treatment with SNE reduced cell viability in a dose-dependent manner in breast cancer cells. Our results showed that treatment of breast cancer cells with 0.1 mg/ml of SNE hypermethylated the VIM, CXCR4 genes and significantly reduced the expression levels of their mRNA (P<0.05). Conclusion: Our findings reveal for the first time the impact of SNE on the methylation of breast cancer cells.

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