scholarly journals Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Click Reaction ◽  
Chemotherapy Drugs ◽  
Targeting Peptide ◽  
And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

scholarly journals tRNA Queuosine Modification Enzyme Modulates the Growth and Microbiome Recruitment to Breast Tumors

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 628
Author(s):  
Jilei Zhang ◽  
Rong Lu ◽  
Yongguo Zhang ◽  
Żaneta Matuszek ◽  
Wen Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
And Migration

Background: Transfer RNA (tRNA) queuosine (Q)-modifications occur specifically in 4 cellular tRNAs at the wobble anticodon position. tRNA Q-modification in human cells depends on the gut microbiome because the microbiome product queuine is required for its installation by the enzyme Q tRNA ribosyltransferase catalytic subunit 1 (QTRT1) encoded in the human genome. Queuine is a micronutrient from diet and microbiome. Although tRNA Q-modification has been studied for a long time regarding its properties in decoding and tRNA fragment generation, how QTRT1 affects tumorigenesis and the microbiome is still poorly understood. Results: We generated single clones of QTRT1-knockout breast cancer MCF7 cells using Double Nickase Plasmid. We also established a QTRT1-knockdown breast MDA-MB-231 cell line. The impacts of QTRT1 deletion or reduction on cell proliferation and migration in vitro were evaluated using cell culture, while the regulations on tumor growth in vivo were evaluated using a xenograft BALB/c nude mouse model. We found that QTRT1 deficiency in human breast cancer cells could change the functions of regulation genes, which are critical in cell proliferation, tight junction formation, and migration in human breast cancer cells in vitro and a breast tumor mouse model in vivo. We identified that several core bacteria, such as Lachnospiraceae, Lactobacillus, and Alistipes, were markedly changed in mice post injection with breast cancer cells. The relative abundance of bacteria in tumors induced from wildtype cells was significantly higher than those of QTRT1 deficiency cells. Conclusions: Our results demonstrate that the QTRT1 gene and tRNA Q-modification altered cell proliferation, junctions, and microbiome in tumors and the intestine, thus playing a critical role in breast cancer development.

scholarly journals Combinatorial nanocarrier based drug delivery approach for amalgamation of anti-tumor agents in breast cancer cells: an improved nanomedicine strategy

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Chandran Murugan ◽  
Kathirvel Rayappan ◽  
Ramar Thangam ◽  
Ramasamy Bhanumathi ◽  
Krishnamurthy Shanthi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Structural Changes ◽  
Silica Nanoparticle ◽  
Therapeutic Effects ◽  
Multiple Drugs

Abstract Combination therapy of multiple drugs through a single system is exhibiting high therapeutic effects. We investigate nanocarrier mediated inhibitory effects of topotecan (TPT) and quercetin (QT) on triple negative breast cancer (TNBC) (MDA-MB-231) and multi drug resistant (MDR) type breast cancer cells (MCF-7) with respect to cellular uptake efficiency and therapeutic mechanisms as in vitro and in vivo. The synthesized mesoporous silica nanoparticle (MSN) pores used for loading TPT; the outer of the nanoparticles was decorated with poly (acrylic acid) (PAA)-Chitosan (CS) as anionic inner-cationic outer layer respectively and conjugated with QT. Subsequently, grafting of arginine-glycine-aspartic acid (cRGD) peptide on the surface of nanocarrier (CPMSN) thwarted the uptake by normal cells, but facilitated their uptake in cancer cells through integrin receptor mediated endocytosis and the dissociation of nanocarriers due to the ability to degrade CS and PAA in acidic pH, which enhance the intracellular release of drugs. Subsequently, the released drugs induce remarkable molecular activation as well as structural changes in tumor cell endoplasmic reticulum, nucleus and mitochondria that can trigger cell death. The valuable CPMSNs may open up new avenues in developing targeted therapeutic strategies to treat cancer through serving as an effective drug delivery podium.

scholarly journals Chemokine CXCL16 Expression Suppresses Migration and Invasiveness and Induces Apoptosis in Breast Cancer Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yeying Fang ◽  
Fraser C. Henderson ◽  
Qiong Yi ◽  
Qianqian Lei ◽  
Yan Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Breast Cancer Cell Lines ◽  
And Migration ◽  
Cxcl16 Expression

Background.Increasing evidence argues that soluble CXCL16 promotes proliferation, migration, and invasion of cancer cellsin vitro. However, the role of transmembrane or cellular CXCL16 in cancer remains relatively unknown. In this study, we determine the function of cellular CXCL16 as tumor suppressor in breast cancer cells.Methods.Expression of cellular CXCL16 in breast cancer cell lines was determined at both RNA and protein levels.In vitroandin vivostudies that overexpressed or downregulated CXCL16 were conducted in breast cancer cells.Results.We report differential expression of cellular CXCL16 in breast cancer cell lines that was negatively correlated with cell invasiveness and migration. Overexpression of CXCL16 in MDA-MB-231 cells led to a decrease in cell invasion and migration and induced apoptosis of the cells; downregulation of CXCL16 in MCF-7 cells increased cell migration and invasiveness. Consistent with thein vitrodata, CXCL16 overexpression inhibited tumorigenesisin vivo.Conclusions.Cellular CXCL16 suppresses invasion and metastasis of breast cancer cellsin vitroand inhibits tumorigenesisin vivo. Targeting of cellular CXCL16 expression is a potential therapeutic strategy for breast cancer.

scholarly journals In VitroandIn VivoEffects of Suppressor of Cytokine Signalling 7 Knockdown in Breast Cancer: The Influence on Cellular Response to Hepatocyte Growth Factor

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Walid Sasi ◽  
Lin Ye ◽  
Wen G. Jiang ◽  
Anup K. Sharma ◽  
Kefah Mokbel
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Xenograft Growth ◽  
And Migration ◽  
Hepatocyte Growth

Purpose. Suppressor of cytokine signaling 7 (SOCS7) is a member of the SOCS family and is known to interact with phospholipase Cγ-1 (PLCγ-1), a key downstream mediator of the hepatocyte growth factor (HGF)/C-MET axis. Here, we report our observations of the effect of knocking down SOCS7 gene on the behaviour of breast cancer cells bothin vitroandin vivoand to elucidate whether this involves HGF/C-MET pathway using the PLCγ-1 blocker U73122.Methods. MCF7 and MDA-MB-231 breast cancer cells were transfected with anti-SOCS7 ribozymal transgene, to create sublines with SOCS7 knockdown. Thein vitrogrowth and migration of the cells were evaluated in basic conditions and with HGF and U73122 treatment using growth assays, scratch-wound, and electrical cell impedance sensing (ECIS) migration assays. MCF7 and MDA-MB-231in vivotumour xenograft growth were also studied.Results. Basalin vitrogrowth and migration of both cellular lines and thein vivoMCF7 xenograft growth were significantly enhanced with SOCS7 knockdown.In vitroHGF treatment has further influenced the growth and migration when SOCS7 gene was knocked-down in both cellular lines(P<0.05). PLCγ-1 pharmacological inhibition of the HGF/C-MET cascade during theirin vitrogrowth and migration seemed to only occur when SOCS7 gene was knocked down.Conclusions. We report a unique regulatory role for SOCS7 in controlling the malignant behaviour of breast cancer lines MCF7 and MDA-MB-231in vitroand the MCF7 tumour xenograftsin vivo. We also report a regulatory role for SOCS7 during thein vitroHGF-induced growth and migration in these cells as HGF treatment and SOCS7 loss have synergistically enhanced these functions. This SOCS7 knockdown-attributed effect could be due to a precise anti-PLCγ-1 role.

Polymer Coated Iron Nanoparticles: Radiolabeling & In Vitro Studies

2020 ◽  
Vol 13 ◽  
Author(s):  
Selin Yılmaz ◽  
Çiğdem İçhedef ◽  
Kadriye Buşra Karatay ◽  
Serap Teksöz
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Iron Oxide ◽  
Cancer Cells ◽  
Iron Oxide Nanoparticles ◽  
Breast Cancer Cells ◽  
Cancer Drug ◽  
Oxide Nanoparticles ◽  
Sem Images

Backgorund: Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively used for targeted drug delivery systems due to their unique magnetic properties. Objective: In this study, it’s aimed to develop a novel targeted 99mTc radiolabeled polymeric drug delivery system for Gemcitabine (GEM). Methods: Gemcitabine, an anticancer agent, was encapsulated into polymer nanoparticles (PLGA) together with iron oxide nanoparticles via double emulsion technique and then labeled with 99mTc. SPIONs were synthesized by reduction–coprecipitation method and encapsulated with oleic acid for surface modification. Size distribution and the morphology of the synthesized nanoparticles were caharacterized by dynamic light scattering(DLS)and scanning electron microscopy(SEM), respectively. Radiolabeling yield of SPION-PLGAGEM nanoparticles were determined via Thin Layer Radio Chromatography (TLRC). Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells in vitro. Results: SEM images displayed that the average size of the drug-free nanoparticles was 40 nm and the size of the drug-loaded nanoparticles was 50 nm. The diameter of nanoparticles were determined as 366.6 nm by DLS, while zeta potential was found as-29 mV. SPION was successfully coated with PLGA, which was confirmed by FTIR. GEM encapsulation efficiency of SPION-PLGA was calculated as 4±0.16 % by means of HPLC. Radiolabeling yield of SPION-PLGA-GEM nanoparticles were determined as 97.8±1.75 % via TLRC. Cytotoxicity of GEM loaded SPION-PLGA were investigated on MDA-MB-231 and MCF7 breast cancer cells. SPION-PLGA-GEM showed high uptake on MCF-7, whilst incorporation rate was increased for both cell lines which external magnetic field application. Conclusion: 99mTc labeled SPION-PLGA nanoparticles loaded with GEM may overcome some of the obstacles in anti-cancer drug delivery because of their appropriate size, non-toxic, and supermagnetic characteristics.

Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

scholarly journals Integrin α3β1 Promotes Invasive and Metastatic Properties of Breast Cancer Cells through Induction of the Brn-2 Transcription Factor

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 480
Author(s):  
Rakshitha Pandulal Miskin ◽  
Janine S. A. Warren ◽  
Abibatou Ndoye ◽  
Lei Wu ◽  
John M. Lamar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Gene Promoter ◽  
Akt Inhibitor ◽  
Integrin Α3β1

In the current study, we demonstrate that integrin α3β1 promotes invasive and metastatic traits of triple-negative breast cancer (TNBC) cells through induction of the transcription factor, Brain-2 (Brn-2). We show that RNAi-mediated suppression of α3β1 in MDA-MB-231 cells caused reduced expression of Brn-2 mRNA and protein and reduced activity of the BRN2 gene promoter. In addition, RNAi-targeting of Brn-2 in MDA-MB-231 cells decreased invasion in vitro and lung colonization in vivo, and exogenous Brn-2 expression partially restored invasion to cells in which α3β1 was suppressed. α3β1 promoted phosphorylation of Akt in MDA-MB-231 cells, and treatment of these cells with a pharmacological Akt inhibitor (MK-2206) reduced both Brn-2 expression and cell invasion, indicating that α3β1-Akt signaling contributes to Brn-2 induction. Analysis of RNAseq data from patients with invasive breast carcinoma revealed that high BRN2 expression correlates with poor survival. Moreover, high BRN2 expression positively correlates with high ITGA3 expression in basal-like breast cancer, which is consistent with our experimental findings that α3β1 induces Brn-2 in TNBC cells. Together, our study demonstrates a pro-invasive/pro-metastatic role for Brn-2 in breast cancer cells and identifies a role for integrin α3β1 in regulating Brn-2 expression, thereby revealing a novel mechanism of integrin-dependent breast cancer cell invasion.

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