scholarly journals MicroRNA-222 promotes drug resistance to doxorubicin in breast cancer via regulation of miR-222/bim pathway

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Hong Dai ◽  
Ling-yun Xu ◽  
Qi Qian ◽  
Qiu-wei Zhu ◽  
Wei-xian Chen
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Malignant Tumors ◽  
Clinical Problem ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Caspase Pathway ◽  
Resistance To Doxorubicin ◽  
Mcf 7

Abstract Resistance to doxorubicin (DOX) is the most common clinical problem in breast cancer therapy, and the underlying molecular mechanism remains to be investigated. MicroRNAs (miRNAs) exhibit important regulatory functions in various malignant tumors including breast cancer. The aim of the present study was to find the relationship between miR-222 and DOX resistance. We found that miR-222 was highly expressed in patients’ serum and DOX-resistant cell line MCF-7-R and that miR-222 could promote proliferation and migration of breast cancer cells. Our results also showed that inhibition of miR-222 in MCF-7-R significantly increased Bcl-2 interacting mediator (Bim) expression both in mRNA and protein levels by using quantitative real-time PCR (qRT-PCR) and Western blot. MTT and flow cytometry suggested that lower expressed miR-222 enhanced apoptosis and decreased IC50 of MCF-7-R cells. Conversely, in MCF-7 cells transfected with miR-222 mimics, up-regulation of miR-222 was associated with decreased Bim level accompanied by less apoptosis and higher IC50. Moreover, miR-222 inhibitors reversed DOX resistance via miR-222-Bim-caspase pathway. Collectively, these data first elucidated that miR-222 could function as an oncogene and was able to reduce the sensitivity of breast cancer cells to DOX through miR-222-Bim-caspase pathway, which provided a potential target to increase DOX sensitivity in clinical breast cancer treatment.

scholarly journals Iron metabolism disturbances in the MCF-7 human breast cancer cells with acquired resistance to doxorubicin and cisplatin

2013 ◽  
Vol 43 (5) ◽  
pp. 1481-1486 ◽  
Author(s):  
VASYL F. CHEKHUN ◽  
NATALIA Yu. LUKYANOVA ◽  
ANATOLIY P. BURLAKA ◽  
NATALIA A. BEZDENEZHNYKH ◽  
SVITLANA I. SHPYLEVA ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Iron Metabolism ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Acquired Resistance ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Resistance To Doxorubicin ◽  
Mcf 7

scholarly journals miR-193b Modulates Resistance to Doxorubicin in Human Breast Cancer Cells by Downregulating MCL-1

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Jingpei Long ◽  
Zhiwei Ji ◽  
Kai Jiang ◽  
Zhaoyang Wang ◽  
Guanmin Meng
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Myeloid Cell ◽  
Untranslated Regions ◽  
Human Breast Cancer Cells ◽  
Cell Leukemia ◽  
Human Breast ◽  
Resistance To Doxorubicin ◽  
Mcf 7

MicroRNAs (miRNAs) family, which is involved in cancer development, proliferation, apoptosis, and drug resistance, is a group of noncoding RNAs that modulate the expression of oncogenes and antioncogenes. Doxorubicin is an active cytotoxic agent for breast cancer treatment, but the acquisition of doxorubicin resistance is a common and critical limitation to cancer therapy. The aim of this study was to investigate whether miR-193b mediated the resistance of breast cancer cells to doxorubicin by targeting myeloid cell leukemia-1 (MCL-1). In this study, we found that miR-193b levels were significantly lower in doxorubicin-resistant MCF-7 (MCF-7/DOXR) cells than in the parental MCF-7 cells. We observed that exogenous miR-193b significantly suppressed the ability of MCF-7/DOXR cells to resist doxorubicin. It demonstrated that miR-193b directly targeted MCL-1 3′-UTR (3′-Untranslated Regions). Further studies indicated that miR-193b sensitized MCF-7/DOXR cells to doxorubicin through a mechanism involving the downregulation of MCL-1. Together, our findings provide evidence that the modulation of miR-193b may represent a novel therapeutic target for the treatment of breast cancer.

scholarly journals Improvement of sensitivity to tamoxifen in estrogen receptor-positive and Herceptin-resistant breast cancer cells

2008 ◽  
Vol 41 (5) ◽  
pp. 367-377 ◽  
Author(s):  
Bin Chen ◽  
Yuanzhong Wang ◽  
Susan E Kane ◽  
Shiuan Chen
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Antiproliferative Effects ◽  
Estrogen Receptor Positive ◽  
Er Positive ◽  
17Β Estradiol

ERBB2 overexpression in estrogen receptor (ER)-positive breast cancer cells such as BT474 (BT) cells has been found to confer resistance to tamoxifen, and suppression of ERBB2 improves the antiproliferative effects of tamoxifen. In this study, the responsiveness to tamoxifen in the BT/HerR, Herceptin-resistant BT cell lines established through constant Herceptin exposure, was evaluated. Compared with BT cells, improvement of sensitivity to tamoxifen in BT/HerR was demonstrated by ER functional analysis and cell proliferation assay. Tamoxifen in the resistant cell line was found to inhibit 17β-estradiol-stimulating estrogen-responsive gene pS2 expression more effectively than in BT cells in real-time PCR assay. Western blot analysis showed that cross-phosphorylation between ER and downstream components of ERBB2 was attenuated in BT/HerR cells. ER redistribution from cytoplasm to nucleus could be found in these cells through immunofluorescence and confocal studies, and importantly, chromatin immunoprecipitation studies demonstrated that tamoxifen induced occupancy of the pS2 promoter by ER and nuclear receptor corepressor (NCOR1) instead of coactivator NCOA3 in these cells. Finally, combination of tamoxifen and Herceptin was found to improve the sensitivity of BT/HerR cells to Herceptin. Our results suggest that the ER genomic pathway in the ER-positive and Herceptin-resistant breast cancer cells may be reactivated, allowing tamoxifen therapy to be effective again, and a combination of tamoxifen and Herceptin can be a potential therapeutic strategy for ER-positive and Herceptin-resistant human breast cancer.

scholarly journals Hesperidin as a preventive resistance agent in MCF–7 breast cancer cells line resistance to doxorubicin

2014 ◽  
Vol 4 (3) ◽  
pp. 228-233 ◽  
Author(s):  
Rifki Febriansah ◽  
Dewi P.P. Dyaningtyas ◽  
Sarmoko ◽  
Nunuk Aries Nurulita ◽  
Edy Meiyanto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Resistance To Doxorubicin ◽  
Line Resistance ◽  
Mcf 7

scholarly journals Hypoxia‐Induced Acidification Causes Mitoxantrone Resistance Not Mediated by Drug Transporters in Human Breast Cancer Cells

2005 ◽  
Vol 27 (1) ◽  
pp. 43-49
Author(s):  
A. E. Greijer ◽  
M. C. de Jong ◽  
G. L. Scheffer ◽  
A. Shvarts ◽  
P. J. van Diest ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Drug Transporters ◽  
Human Breast ◽  
Protein Levels ◽  
Resistance To Doxorubicin ◽  
Resistance To Chemotherapy ◽  
Mcf 7

Hypoxia has clinically been associated with resistance to chemotherapy. The aim of this study was to investigate whether hypoxia induces resistance to doxorubicin and mitoxantrone, two common drugs in cancer treatment, in MCF‐7 breast cancer cells, and SW1573 non‐small lung cancer cells. In addition, the role of drug transporters P‐gp, BCRP and MRP1 was analysed. Hypoxia induced resistance in MCF‐7 cells to mitoxantrone shifted the IC50 value from 0.09 μM (±0.01) to 0.54 μM (±0.06) under hypoxia, whereas survival of MCF‐7 and SW1573 cells in the presence of doxorubicin was not altered. Accumulation of mitoxantrone and daunorubicin, a doxorubicin fluorescent homologue, appeared to be 5.3 and 3.2 times lower in MCF‐7 cells, respectively. Cytotoxicity assays showed no increased functionality of the drug transporters P‐gp, BCRP and MRP1 under hypoxia. In addition, protein levels of these drug transporters were not changed. Medium of the MCF‐7 cells became more acidic under hypoxia thereby causing a decreased uptake of mitoxantrone. Hypoxia induces mitoxantrone resistance in MCF‐7 cells not mediated by the three major MDR transporters. Hypoxia‐induced acidification may cause this resistance by decreased cellular uptake together with a lowered cytotoxicity due to pH‐dependent topoisomerase type II activity.

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