Abstract:
Objective:To investigate the influence of cisplatin (DDP) combined with all-trans retinoic acid (ATRA) on the growth and apoptosis of human non-small cell lung cancer A549 cell line and on the expression of Survivin mRNA and COX-2 mRNA in this cell line in vitro. Methods:Different concentrations of DDP (0.5mg/L, 5mg/L, and 50mg/L), different concentrations of ATRA (0.1 μ mol /L, 1 μ mol /L, and 10μ mol /L) and DDP combined wi th ATRA (DDP 5mg/L and ATRA1 μ mol /L) were used in cultures for the pulmonary carcinoma A 549 cell line in different groups. The influence on A 549 growth induced by different concentrations of DDP, different concentrations of ATRA, and DDP combined with ATRA were analyzed by MTT assay. Expression of Survivin mRNA and COX- 2 mRNA levels in the A549 cells were detected by R-T PCR before and after treatment. Flow cytometry (Annexin V-FITC/PI Staining Methods) was used to determine the apoptosis index of the A 549 cells before and after treatment. Results: DDP alone or ATRA alone was found to inhibit the proliferation of the A549 cells ( P<0.05), and the apoptotic effect was increased in a concentration-dependent manner (P<0.05). Compared with DDP alone, DDP combined with ATRA significantly inhibited the proliferation of the A 549 cells ( P<0.05), increased the apotosis rate of the cells and suppressed Survivin mRNA and COX-2 mRNA expression in the cells ( P<0.05). Flow cytometry results showed that the early apoptosis rate, middle and late apoptosis rate and secondary necrosis rate in the DDP combined with ATRA group were (7.37± 3.83)%, (34.37± 2.08)%, and (7.44± 0.46)%, respectively, higher than those of the DDP group ( 3.55± 0.75)%, (6.62± 0.33)%, and (3.03± 0.05)%, P<0.05. Conclusion:ATRA can significantly increase the chemosensitivity of human non-small cell lung cancer cells to DDP. The mechanism may be related to inhibition of Survivin mRNA and COX-2 mRNA expression.