PI3K/Akt inhibition and down-regulation of BCRP re-sensitize MCF7 breast cancer cell line to mitoxantrone chemotherapy | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 7، دوره 18، شماره 5، مرداد 2015، صفحه 472-477 اصل مقاله (1.52 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2015.4410 | ||
| نویسندگان | ||
| Tahereh Komeili-Movahhed1، 2؛ Shamileh Fouladdel1؛ Elmira Barzegar1؛ Shekoufeh Atashpour1؛ Mohammad Hossein Ghahremani3، 4؛ Seyed Nasser Ostad3؛ Zahra Madjd5؛ Ebrahim Azizi* 1 | ||
| 1Molecular Research Laboratory, Department of Pharmacology and Toxicology, Tehran University of Medical Sciences, Tehran, Iran | ||
| 2Cellular and Molecular Research Center, Qom University of Medical Sciences, Qom, Iran | ||
| 3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran | ||
| 4Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran | ||
| 5Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran | ||
| چکیده | ||
| Objective(s):Multidrug resistance (MDR) of cancer cells is a major obstacle to successful chemotherapy. Overexpression of breast cancer resistance protein (BCRP) is one of the major causes of MDR. In addition, it has been shown that PI3K/Akt signaling pathway involves in drug resistance. Therefore, we evaluated the effects of novel approaches including siRNA directed against BCRP and targeted therapy against PI3K/Akt signaling pathway using LY294002 (LY) to re-sensitize breast cancer MCF7 cell line to mitoxantrone (MTX) chemotherapy. Materials and Methods: Anticancer effects of MTX, siRNA, and LY alone and in combination were evaluated in MCF7 cells using MTT cytotoxicity assay and flow cytometry analysis of cell cycle distribution and apoptosis induction. Results: MTT and apoptosis assays showed that both MTX and LY inhibited cell proliferation and induced apoptosis in MCF7 cells. Results indicated that inhibition of BCRP by siRNA or PI3K/Akt signaling pathway by LY significantly increased sensitivity of MCF7 cells to antiproliferation and apoptosis induction of MTX. Furthermore, MTX showed G2/M arrest, whereas LY induced G0/G1 arrest in cell cycle distribution of MCF7 cells. Combination of siRNA or LY with MTX chemotherapy significantly increased accumulation of MCF7 cells in the G2/M phase of cell cycle. Conclusion: Combination of MTX chemotherapy with BCRP siRNA and PI3K/Akt inhibition can overcome MDR in breast cancer cells. This study furthermore suggests that novel therapeutic approaches are needed to enhance anticancer effects of available drugs in breast cancer | ||
| کلیدواژهها | ||
| Breast Cancer؛ BCRP؛ Combination therapy؛ Mitoxantrone؛ PI3K/Akt؛ siRNA | ||
| مراجع | ||
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