Inhibition Of MACC1 Expression Enhances Sensitivity Of Non-small Cell Lung Cancer A549 Cells To Cisplatin Chemotherapy

[Objective]: Patients with advanced non-small cell lung cancer lose the opportunity to operate,chemotherapy is a standardized treatment for patients.In recent years,a variety of new anti-cancer drugs have been applied to the clinic.However,the dilemma of chemical drugs for anti-cancer is that once a certain anti-cancer drug is used for a long time,it is easy to produce drug resistance and cause a failure of treatment.How to reverse the drug resistance of tumor cells seems to have the great significance of clinical guidance and treatment.This study will conduct a preliminary study on the expression level of MACC1 in A549 cells of drug-resistant lung cancer and the influence mechanism of drug resistance,and thus to reverse the drug resistance.[Methods]:(1)To develop drug resistant and non-drug resistant NSCLC A549 cells,and investigate the expression level of MACC1 mRNA about them by means of RT-PCR;(2)To inhibit the expression of MACC1 in drug resistant cells,continue to deal cells with cisplatin,and then investigate the influence of cell proliferation inhibition rate by MTT method;(3)Using Hoechst33258 staining method to analyze the apoptotic state of drug-resistant A549 cells after MACC1 inhibition;(4)After inhibiting the expression of MACC1,the expression changes of p-gp resistant glycoproteins,e-cadherin and n-cadherin treated by cisplatin being detected by Western blot;(5)The change of migration ability after cisplatin treatment of A549 cells being investigated by Transwell experiment.[Results]:(1)The RT-PCR detection about the expression level of MACC1 mRNA in drug resistant NSCLC A549 cells and non-drug resistant NSCLC A549 cells shows that in the drug-resistant A549 cells,the MACC1 mRNA expression level was significantly higher than the non-drug resistant of A549 cells(p < 0.05);(2)To inhibit the expression of MACC1 in drug resistant A549 cells by using cisplatin,the results showed that the proliferation inhibition rate of A549 cells increased significantly(p<0.05);(3)After the expression of MACC1 in drug-resistant A549 cells was inhibited,half of cisplatin's effective concentration(IC50)was reduced to 17.89?mol/L,and the control group IC50 was 110.18?mol/L,two of which was a significant difference(p <0.05);(4)Using the Hoechst33258 cell staining showed that after inhibition of MACC1 expression in A549 cells,the effect of cell nucleus concentration and staining enhancement was obvious,and the cell morphology showed cell apoptosis;(5)After inhibiting the expression of MACC1 in A549 cells,Western blot results showed that the expression levels of e-cadherin and n-cadherin in A549 cells were significantly changed,and the invasion and metastasis ability of cells significantly decreased(p < 0.05);(6)Transwell experiment showed that the migration ability of NSCLC cells was significant(p < 0.05)after inhibition of MACC1 expression in A549 cells.[Conclusion]:The abnormal increase of MACC1 in drug resistant A549 cells may be one of the molecular mechanisms of drug resistance in lung cancer cells.siRNA-MACC1 can effectively transfect the drug-resistant A549 cells,and can effectively inhibit the expression of MACC1.After tansfection in different concentration of siRNA MACC1,the P-gp protein expression level in cells and siRNA MACC1 transfection concentration shows correlation.The inhibition of MACC1 can affect the expression of P-gp in the cell,so as to realize the reversal of the cell resistance.In addition,the inhibition of MACC1 could significantly reduce the invasion and migration ability of A549 cells.