Effects of Simvastatin on Expression of Multidrug Resistance Gene and Protein of SHI-1 Cells

Abstract

To investigate the effects of simvastatin(SIM) and serum free medium(SFM) on the expression of multidrug resistance gene(MDR1) and protein of SHI-1 cells. Trypan blue exclusion assay was used to detect the proliferation level and viability of SHI-1 cells after treatment with SIM and culture in SFM; The multi-drug resistant protein p-gp was measured by flow cytometry after culture in SFM for 1 to 3 days and treatment with various concentration of simvastatin. The effect of SFM culture and SIM treatment on the expression of MDR1 trascript was detected by qPCR; ELISA was used to measure the change of cellular cholesterol after culture in SIM and SFM. Chemosensitivity assay was performed after treatment with SIM for SHI-1 cells. Compared with control group, the growth of SHI-1 cells cultured in SFM decreased in a time-dependent manner. The growth-inhibitory effect was markedly increased when SHI-1 cells were treated with SIM and SFM. The mRNA level of MDR1 gene decreased after SIM treatment or/and culture in SFM. P-gp protein was downregulated in SHI-1 cells cultured in SFM or/and treated with SIM. The cellular cholesterol level increased when the cells were cultured in SFM. Total cellular cholesterol level decreased in SHI-1 cells treated with SIM and cultured in SFM. Chemosensitivity assays found that pre-treatment with SIM could increase the cytotoxicity of DNR to SHI-1 cells. Culture with SIM and SFM can downregulate the expression of MDR1 gene and p-gp protein in SHI-1 cells. SIM also can enhance the chemotherapeutic sensitivity of SHI-1 cells.