MACC1 overexpression induces cisplatin resistance in lung adenocarcinoma A549 cells by activating c-Met/Akt pathway

The overexpression of metastasis-associated in colon cancer-1 (MACC1) was correlated with poor prognosis in non-small cell lung cancer (NSCLC), and the development of cisplatin (CDDP) resistance was a frequent event in lung adenocarcinoma therapy. This study aimed to investigate the role of MACC1 in CDDP resistance in human lung adenocarcinoma A549 cells. We first established a CDDP-resistant A549/CDDP cell line from its parental cell line A549. The chemoresistance was confirmed by CCK-8 assay, western blotting of apoptotic proteins and colony formation assay. The CDDP sensitivity of A549 cell after ectopic overexpression of MACC1 by introducing MACC1-expressing cDNA was also determined. Then MACC1 shRNA plasmids and negative control plasmids were transfected into A549/CDDP cells for further researches. We found that A549/CDDP cells developed CDDP resistance following continuous exposure to CDDP. MACC1 was up-regulated in A549/CDDP cells, while the overexpression of MACC1 also induced CDDP resistance in A549 cells. The inhibition of MACC1 in A549/CDDP cells reversed CDDP resistance by inducing apoptosis after CDDP treatment. The mechanism underlying MACC1 induced CDDP resistance was also investigated. We found that c-Met and P-Akt increased in A549/CDDP cells, while the inhibition of c-Met and P-Akt reversed CDDP resistance. In conclusion, we found that MACC1 overexpression induced CDDP resistance in A549 cells by activating c-Met/Akt pathway.