Pristimerin Contributes to Gefitinib Resistance in Lung Cancer Cells by regulating microRNA-936 expression

Abstract

To investigate the effect of pristimerin on gefitinib resistance in lung cancer cells and its regulation on microRNA-936. Lung cancer cell HCC827 was cultured in vitro , lung cancer gefitinib resistant cell HCC827/gefitinib resistant was established and HCC827/gefitinib resistant cells were randomly assigned to control group, pristimerin-L group, pristimerin-M group, pristimerin-H group, gefitinib group, gefitinib+pristimerin group, gefitinib+microRNA-negative control group, gefitinib+microRNA-936 group, gefitinib+pristimerin+anti-microRNA negative control group and gefitinib+pristimerin+anti-microRNA-936 group. 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide was used to detect the inhibition rate of cell proliferation, as well as the median half-maximal inhibitory concentration; the expression amount of microRNA-936 was detected by quantitative reverse transcription-polymerase chain reaction; cell migration and invasion were detected by transwell chamber assay. Compared with HCC827 cells, the proliferation inhibition rate of HCC827/gefitinib resistant cells was significantly lower and the half-maximal inhibitory concentration value was significantly higher (p<0.05); compared with the control group, the inhibition rate of cell proliferation was increased, the half-maximal inhibitory concentration value was decreased and the expression of microRNA-936 was increased (p<0.05) in pristimerin-L group, pristimerin-M group and pristimerin-H group; compared with the gefitinib group, the inhibition rate of cell proliferation was higher and the number of migration and invasion cells decreased in the gefitinib+pristimerin group (p<0.05); compared with the gefitinib+microRNA negative control group, the gefitinib+microRNA-936 group showed higher cell proliferation inhibition rate and lower cell number in migration and invasion (p<0.05); compared with the gefitinib+pristimerin+anti-microRNA negative control group, the cell proliferation inhibition rate decreased and the migration and invasion cell numbers increased in the gefitinib+pristimerin+anti-microRNA-936 group (p<0.05). Pristimerin may enhance cell gefitinib sensitivity by inhibiting proliferation, migration and invasion of gefitinib resistant cells in lung cancer by up regulating microRNA-936 expression.