The Effect Of Apigenin On Cell Proliferation And Toxicity In Response To Therapeutic Drugs In Non-Small Cell Lung Cancer Cells

Firstly, we studied the anti-tumor effects of apigenin on 4 types of non-small cell lung cancer (NSCLC) cell lines (A549, H460, LTEP-a2 and H292).The result showed that apigenin significantly inhibited the proliferation of the NSCLS cells, and increased the susceptibility of the NSCLS cells to 2 kinds of anti-tumor drugs(Oxaliplatin, Bleomyicin). Therefore, apigenin is promising for NSCLS treatment.Secondly, we investigated the mechanism of apigenin-dependent increased susceptibility. After the 4 types of NSCLS cells were treated with apigenin, the results of Western blotting revealed the significant reduction of Nrf2 and Nrf2-mediated genes(HO-1,NQO1 and AKR1C). This proved that in NSCLS cells, apigenin can inhibit Nrf2 signal pathway. As the Nrf2-mediated cytoprotective proteins such as phaseâ…¡detoxifying enzymes (e.g. HO-1,NQ01 and AKR1C) and drug efflux pumps protect cells against oxidative stress and xenobiotics, we hypothesized that apigenin probably inhibited Nrf2 pathway to sensitize the NSCLS cells. To verify the hypothesis, we established stable cell lines with Nrf2 down-regulated. Nrf2 down-regulated cell lines A549-C27 were obtained by screening A549 and H460 cells transfected with shRNA-Nrf2 through Western blotting detection. In A549-C27 cells, compared to the control cells, the sensitization effect of apigenin was obviously weaker. As a result, we proved that the inhibition of Nrf2 pathway by apigenin contributed to the increased susceptibility of NSCLS cells to anti-tumor drugs.This research not only confirmed the anti-tumor effects of apigenin on NSCLS cells, but also indicated the potential application of apigenin combined with anti-tuomr drugs in clinical treatment for NSCLS and provided new evidence for the study on the relationship between Nrf2-ARE signal pathway and tumor drug resistance.