Effects of collagen IV on chemotherapy-induced apoptosis of cisplatin-resistant human lung adenocarcinoma cells

Objective:To investigate effects of collagen Ⅳ (CⅣ) in extracelluar matrix (ECM) on sensitivity and apoptosis of drug-resistant non small cell lung cancer (NSCLC) cells and to elucidate the role of phosphatidylinositol 3′kinase(PI3-K) in the signaling pathway. Methods:Cisplatin(DDP)-resistant human lung adenocarcinoma cell line A549/DDP were cultured in RPMI 1640 medium supplemented with 10% fetal calf serum in vitro. DDP 6 μmol/L was added to maintain the drug resistant phenotype of the cells. The inhibitory effects of DDP and/or LY294002(PI3-K inhibitor) on cell proliferation were tested by MTT assay. Cell adhesion rate was measured by cell adhesion experiments. Flow cytometry was applied to study the influence of CⅣ and LY294002 on apoptosis of A549/DDP cells before and after DDP treatment. Results: Adhesion of A549/DDP cells was significantly increased in CⅣ group and polylysine (PLL) group compared with control group (without CⅣ coating,P0.001), but adhesion of fibronectin (FN) in the two groups had no significant difference compared with control group(P0.05). The 50% inhibitory concentration (IC 50) of DDP was significantly increased from 169.9 μmol/L to 258.3 μmol/L by pre-coating with CⅣ. LY294002 significantly blocked the anti-apoptotic effects of CⅣ against DDP. IC 50 value of DDP was reduced to 87.1 μmol/L(P 0.05). Conclusion:CⅣ was involved in the induction of drug-resistance of NSCLC. PI3-K was one of the signaling pathways.