Effects of SLC22a18 over-expression on sensitivity to chemotherapeutic agents in human breast cancer cell MCF-7

Abstract

Objective To study the effects of SLC22a18 over-expression on sensitivity to paclitaxel,adriamycin,cyclophosphamide,mitoxantone and DDP in human breast cancer cell MCF-7,and to research the function and the mechanism of multidrug resistance of the gene.Methods The eukaryotic expression plasmid pIRES2-EGFP-SLC22a18 was constructed and transfected into MCF-7 cells by Lipofectamine2000.The sensitivity of MCF-7 cells to chemotherapeutic agents was studied by CCK-8 assay.Flow cytometry was used to analyze the cell cycles of MCF-7 cells and the adriamycin accumulation in cells with SLC22al8 over-expression.Results CCK-8 assay showed that the over-expression of SLC22al8 reduced the sensitivity while increased the IC50 to paclitaxel(t = 3.13,P ＜ 0.05),cyclophosphamide(t =3.63,P ＜ 0.05),and mitoxantone(t = 4.51,P ＜ 0.05)respectively in MCF-7 cells,but increased the sensitivity and decreased the IC50 to DDP(t = 4.23,P ＜ 0.05).The sensitivity and IC50 to adriamycin were not changed significantly(t = 1.47,P ＞ 0.05).The over-expression of SLC22al8 in MCF-7 cells led to an increase of G0/G1 cell population(59.71% to 56.03%,X2 = 21.85,P ＜ 0.05),and a decrease of S cell population(37.20% to 40.30%,X2 = 16.06,P ＜ 0.05)and G2/M cell population(3.08% to 3.67%,X2 =4.06,P ＜ 0.05)compared to control,indicating that SLC22AI8 might inhibit the proliferation of cancer cells.FCM also revealed that the accumulation of adriamycin in MCF-7 cells with SLC22al8 over-expression was significantly decreased compared to control(t = 3.07,P ＜ 0.05).Conclusion The over-expression of SLC22al8 reduced the sensitivity to paclitaxel,cyclophosphamide,and mitoxantone,and increased the sensitivity to DDP in human breast cancer MCF-7 cells.Gene SLC22al8 may inhibit the proliferation of cancer cells,and may lead to multidrug resistance by decreasing the accumulation of chemotherapeutic agents in cells. Key words: Breast carcinoma; Drug sensitivity; Multidrng resistance