Reductive responsive micelle overcoming multidrug resistance of breast cancer by co-delivery of DOX and specific antibiotic

2019 ◽  
Vol 7 (40) ◽  
pp. 6075-6086 ◽  
Author(s):  
Yani Cui ◽  
Yuedi Yang ◽  
Mengcheng Ma ◽  
Yang Xu ◽  
Junhui Sui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Combination Chemotherapy ◽  
Broad Spectrum ◽  
Antitumor Drug ◽  
Chemotherapy Strategy ◽  
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The redox-degradable nano-micelle-reversed drug resistance by combination chemotherapy strategy of salinomycin (SL) that could specifically inhibit A/MCF-7 cells and a traditional broad-spectrum antitumor drug, doxorubicin (DOX).

scholarly journals SH003 reverses drug resistance by blocking signal transducer and activator of transcription 3 (STAT3) signaling in breast cancer cells

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Hye-Sook Seo ◽  
Jin Mo Ku ◽  
Hee-Jae Lee ◽  
Jong-Kyu Woo ◽  
Chunhoo Cheon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cell Growth ◽  
Cancer Patients ◽  
Breast Cancer Cells ◽  
Signal Transducer ◽  
Stat3 Signaling ◽  
Transcription 3 ◽  
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Overcoming drug resistance is an important task for investigators and clinician to achieve successful chemotherapy in cancer patients. Drug resistance is caused by various factors, including the overexpression of P-glycoprotein (P-gp, MDR1). The development of new, useful compounds that overcome drug resistance is urgent. SH003 is extracted from the mixture of three different herbs, and its anticancer effect has been revealed in different cancer cell types. In the present study, we investigated whether SH003 is able to reverse drug resistance using paclitaxel-resistant breast cancer cells (MCF-7/PAC). In our experiments, SH003 significantly decreased cell growth and colony formation in MCF-7/PAC cells and parental MCF-7 cells. This growth inhibition was related to the accumulation of cells in the sub-G0/G1 apoptotic population and an increase in the number of apoptotic cells. SH003 reduced the mRNA expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated proteins (MRPs) in MCF-7/PAC cells. SH003 also down-regulated the expression of P-gp. SH003 reversed drug efflux from MCF-7/PAC cells, resulting in rhodamine123 (Rho123) accumulation. Inhibition of drug resistance by SH003 is related to the suppression of the signal transducer and activator of transcription 3 (STAT3) signaling pathway. SH003 decreased STAT3 activation (p-STAT3) and its nuclear translocation and inhibited the secretion of VEGF and MMP-2, which are STAT3 target genes. An STAT3 inhibitor, JAK inhibitor I and an HIF-1α inhibitor decreased cell growth in MCF-7 and MCF-7/PAC cells. Taken together, these results demonstrate that SH003 can overcome drug resistance, and SH003 might be helpful for chemotherapy in cancer patients.

Study of the mechanism responsible for multidrug resistance in breast cancer MCF-7 cell mediated by 14-3-3σ

2010 ◽  
Vol 34 (8) ◽  
pp. S47-S47
Author(s):  
Guopei Zheng ◽  
Sisi Yi ◽  
Yafei Li ◽  
Fangren Kong ◽  
Yanhui Yu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Mcf 7

scholarly journals ARTEMISININ MODULATING EFFECT ON HUMAN BREAST CANCER CELL LINES WITH DIFFERENT SENSITIVITY TO CYTOSTATICS

2017 ◽  
Vol 39 (1) ◽  
pp. 25-29 ◽  
Author(s):  
V F Chekhun ◽  
N Yu Lukianova ◽  
T Borikun ◽  
T Zadvornyi ◽  
A Mokhir
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Iron Homeostasis ◽  
Chemotherapeutic Agents ◽  
Fold Change ◽  
Breast Cancer Cell Lines ◽  
Cellular Iron ◽  
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Aim: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin — Dox; cisplatin — DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. Materials and Methods: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid. The latter was added to modulate iron levels in the cells and explore its role in artemisinin-induced effects. The MTT assay was used to monitor cell viability, whereas changes of expression of selected proteins participating in regulation of cellular iron homeostasis were estimated using immunocytochemical methods. Finally, relative expression levels of miRNA-200b, -320a, and -34a were examined by using qRT-PCR. Results: Artemisinin affects mechanisms of the resistance of breast cancer cells towards both Dox and DDP at sub-toxic doses. The former drug induces changes of expression of iron-regulating proteins via different mechanisms, including epigenetic regulation. Particularly, the disturbances in ferritin heavy chain 1, lactoferrin, hepcidin (decrease) and ferroportin (increase) expression (р ≤ 0.05) were established. The most enhanced increase of miRNA expression under artemisinin influence were found for miRNA-200b in MCF-7/DDP cells (7.1 ± 0.98 fold change), miRNA-320a in MCF-7/Dox cells (2.9 ± 0.45 fold change) and miRNA-34a (1.7 ± 0.15 fold change) in MCF-7/S cells. It was observed that the sensitivity to artemisinin can be influenced by changing iron levels in cells. Conclusions: Artemisinin can modify iron metabolism of breast cancer cells by its cytotoxic effect, but also by inducing changes in expression of iron-regulating proteins and microRNAs (miRNAs), involved in their regulation. This modification affects the mechanisms that are implicated in drug-resistance, that makes artemisinin a perspective modulator of cell sensitivity towards chemotherapeutic agents in cancer treatment.

scholarly journals Induction of multidrug resistance associated protein 2 in tamoxifen-resistant breast cancer cells

2007 ◽  
Vol 14 (2) ◽  
pp. 293-303 ◽  
Author(s):  
Hoo Kyun Choi ◽  
Jin Won Yang ◽  
Sang Hee Roh ◽  
Chang Yeob Han ◽  
Keon Wook Kang
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Transcriptional Activation ◽  
Breast Cancer Cells ◽  
Pregnane X Receptor ◽  
Pi3 Kinase ◽  
Gene Promoters ◽  
Breast Cancer Patients ◽  
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Acquired resistance to tamoxifen (TAM) is a serious therapeutic problem in breast cancer patients. The transition from chemotherapy-responsive breast cancer cells to chemotherapy-resistant cancer cells is mainly accompanied by the increased expression of multidrug resistance-associated proteins (MRPs). In this study, it was found that TAM-resistant MCF-7 (TAMR-MCF-7) cells expressed higher levels of MRP2 than control MCF-7 cells. Molecular analyses using MRP2 gene promoters supported the involvement of the pregnane X receptor (PXR) in MRP2 overexpression in TAMR-MCF-7 cells. Although CCAAT/enhancer-binding protein β was overexpressed continuously in TAMR-MCF-7 cells, this might not be responsible for the transcriptional activation of the MRP2 gene. In addition, the basal activities of phosphatidylinositol 3-kinase (PI3-kinase) were higher in the TAMR-MCF-7 cells than in the control cells. The inhibition of PI3-kinase significantly reduced both the PXR activity and MRP2 expression in TAMR-MCF-7 cells. Overall, MRP2 induction plays a role in the additional acquisition of chemotherapy resistance in TAM-resistant breast cancer.

The underlying mechanism contributing to P-gp over-expression and drug resistance in the MCF-7 breast cancer cells induced by adriamycin.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12028-e12028
Author(s):  
Guangji Wang ◽  
Jiye Aa ◽  
Chun Ge
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Underlying Mechanism ◽  
Ros Generation ◽  
Down Regulation ◽  
Over Expression ◽  
And Function ◽  
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e12028 Background: Continuous exposure of breast cancer cells to adriamycin (ADR) induces the over-expression of P-glycoprotein (P-gp) and multiple drug resistance. However, the biochemical process and underlying mechanisms are not clear. Our previous study revealed that ADR increased reactive oxygen species (ROS) generation and reduced glutathione (GSH) biosynthesis, while N-acetylcysteine, the ROS scavenger, reversed the over-expressed P-gp induced by ADR. Methods: Based on MCF-7 breast cancer cells and the adriamycin-resistant MCF-7 subline (MCF-7R), we investigated the P-gp expression on mRNA, protein and function level by qPCR, western blotting, flow cytometry and laser scanning confocal and so on, under SLC7A11 down-regulation/over-expression, cystine depletion/supplement, increased ROS generation and combined factors. Results: The present study showed that ADR inhibited cystine influx (source material of GSH) and SLC7A11 transporter (in charge of cystine uptake) in MCF-7 cells. For the first time, we showed that a down-regulation/silence of SLC7A11, or cystine deprivation, or an enhanced exposure of ROS agents directly and significantly increased P-gp expression; yet, a combination of either an inhibited/silenced SLC7A11 or cystine deprivation and an increased ROS dramatically promoted the P-gp expression in MCF-7 cells. On the contrary, an over-expression of SLC7A11, or sufficiently supplementary cystine, or scavenger of ROS significantly depressed P-gp expression and activity. Moreover, the down-regulation of SLC7A11 and cystine deprivation induced an elevation of ROS and P-gp that could be reversed by N-acetylcysteine. It was suggested that ROS and SLC7A11/cystine were the two relevant factors responsible for the upregulated expression and function of P-gp. Conclusions: This study provided the direct evidences suggesting that ROS triggered over-expression of P-gp and demonstrated that the combination of either an inhibition of SLC7A11 or cystine influx and elevated ROS was the underlying mechanism contributing to P-gp over-expression induced by ADR. It was indicated that the SLC7A11 might be a potential target modulating ADR resistance.

Delivery of siRNA by MRI-visible nanovehicles to overcome drug resistance in MCF-7/ADR human breast cancer cells

Biomaterials ◽  
2014 ◽  
Vol 35 (35) ◽  
pp. 9495-9507 ◽  
Author(s):  
Gan Lin ◽  
Wencheng Zhu ◽  
Li Yang ◽  
Jun Wu ◽  
Bingbing Lin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

scholarly journals Psoralen reverses the P-glycoprotein-mediated multidrug resistance in human breast cancer MCF-7/ADR cells

2016 ◽  
Vol 13 (6) ◽  
pp. 4745-4750 ◽  
Author(s):  
JINGRU JIANG ◽  
XIAOHONG WANG ◽  
KAI CHENG ◽  
WANZHONG ZHAO ◽  
YITONG HUA ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
Human Breast Cancer ◽  
Human Breast ◽  
P Glycoprotein ◽  
Mcf 7

scholarly journals Doxorubicin induces drug resistance and expression of the novel CD44st via NF-κB in human breast cancer MCF-7 cells

2014 ◽  
Vol 31 (6) ◽  
pp. 2735-2742 ◽  
Author(s):  
XIN JIAN FANG ◽  
HUA JIANG ◽  
YA QUN ZHU ◽  
LI YUAN ZHANG ◽  
QIU HONG FAN ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Human Breast Cancer ◽  
The Novel ◽  
Human Breast ◽  
Mcf 7

scholarly journals ELOVL2: a novel tumor suppressor attenuating tamoxifen resistance in breast cancer

2020 ◽  
Author(s):  
Dawoon Jeong ◽  
Juyeon Ham ◽  
Hyeon Woo Kim ◽  
Heejoo Kim ◽  
Hwee Won Ji ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Patients ◽  
Tumor Tissue ◽  
Tamoxifen Resistance ◽  
Colony Formation Assay ◽  
Breast Cancer Patients ◽  
Methylation Analysis ◽  
Genome Wide ◽  
Mcf 7

Abstract Background To comprehensively understand the molecular mechanism of tamoxifen resistance (TamR) acquisition by epigenetically regulated genes, it is essential to identify pivotal genes by genome-wide methylation analysis and verify their function in xenograft animal model and cancer patients. Methods The MCF-7/TamR breast cancer cell line was developed and a genome-wide methylation array was performed. The methylation and expression of ELOVL2 was validated in cultured cells, xenografted tumor tissue, and breast cancer patients by methylation-specific PCR, qRT-PCR, Western blot analysis, and immunohistochemistry. Deregulation of ELOVL2 and THEM4 was achieved using siRNA or generating stable transfectants. Tam sensitivity, cell growth, and apoptosis were monitored by colorimetric and colony formation assay and flow cytometric analysis. Pathway analysis was performed to generate networks for the differentially methylated genes in the MCF-7/TamR cells and for the differentially expressed genes in the ELOVL2-overexpressing cells. Results Genome-wide methylation analysis in the MCF-7/TamR cells identified elongation of very-long chain fatty acid protein 2 (ELOVL2) to be significantly hypermethylated and downregulated, which was further verified in the tumor tissues from TamR breast cancer patients (n = 28) compared with those from Tam-sensitive (TamS) patients (n = 33) (P < 0.001). Immunohistochemical analysis of tissues from cancer patients showed lower expression of ELOVL2 in the TamR than TamS tissues. Growth of the MCF-7/TamR cells overexpressing ELOVL2 was retarded in cell culture and also in xenograft tumor tissue. Strikingly, ELOVL2 attenuated resistance to Tam up to 70% judged by the colorimetric and colony formation assay and xenograft mouse model. ELOVL2 contributed to the recovery of Tam sensitivity by regulating a group of genes in the AKT and ERα signaling pathways, e.g., THEM4, which plays crucial roles in drug resistance. Conclusions ELOVL2 was hypermethylated and downregulated in TamR breast cancer patients compared with TamS patients. ELOVL2 is responsible for the recovery of Tam sensitivity. AKT- and ERα-hubbed networks are pivotal in ELOVL2 signaling, where THEM4 contributes to the relaying ELOVL2 signaling. This study implies that deregulation of a gene in fatty acid metabolism can lead to drug resistance, giving insight into the development of a new therapeutic strategy for drug-resistant breast cancer.

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