Cytoplasmic M-CSF Induced Chemoresistance Of MCF-7is Mediated By Regulation Of Autophagy And Apoptosis

ObjectiveTo verify M-CSF induced chemoresistance of MCF-7cells. To clarifythe effect of M-CSF on autophagy and apoptosis of MCF-7cells. Toexplore whether M-CSF induce chemoresistance of MCF-7thoughregulating autophagy and apoptosis.MethodsMCF-7, MCF-7-C and MCF-7-M cells were maintained in RPMI1640supplemented with10%NBCS. The efficiency of M-CSFtransfection of MCF-7cells was analyzed by Western blot. The effect ofM-CSF on chemoresistance of MCF-7cells was analyzed by MTT assay.The effect of M-CSF on apoptosis of MCF-7cells and its relatedmechanisms were analyze by Western blot, Hoechst33342staining andflow cytometry. Western blot and MTT were used to explore the effect ofM-CSF on autophagy of MCF-7cells and also the relationship betweenchemoresistance and autophagy.ResultsThe results from MTT assay showed that the adriamycin(ADM) orcisplatin(CDDP) sensitivity of MCF-7-M cells is decreased comparedwith either MCF-7or MCF-7-C cells and LY294002, SH-6or YM155 enhances chemosensitivity of MCF-7-M cells (p<0.01). The results fromHoechst33342staining assay and flow cytometry showed that theapoptosis rate is lower in MCF-7-M cells compared with either MCF-7cells or MCF-7-C cells and LY294002, SH-6or YM155increases theapoptosis rate of MCF-7-M cells (p<0.01). The results from western blotshowed that the experssion level of PI3K, p-PI3K, Akt, p-Akt andSurvivin are higher in MCF-7-M cells compared with control cells andLY294002or SH-6significantly inhibits the experssion of p-Akt andSurvivin in MCF-7-M cells(p<0.01). The autophagy level is higher inADM or CDDP treated MCF-7-M cells compared with control cells(p<0.01). And MCF-7-M encounter autophagic cell death under ADM orCDDP treatment.ConclusionM-CSF induced chemoresistance is mediated by apoptosis inhibitionthrough activating PI3K/Akt/Survivin pathway in MCF-7cells. M-CSFcan induce autophagic cell death in doxorubicin or cisplatin treatedMCF-7cells.