Effects of tramadol on the proliferation, apoptosis and cell cycle of human lung adenocarcinoma A549 cells / 医学研究生学报

ABSTRACT

Objective Few reports are seen domestically on the effect of tramadol (TMD) on the growth and metastasis of lung cancer cells. This study was to investigate the effect of TMD on the proliferation, apoptosis and cell cycle of human lung adenocarcinoma (LAC) A549 cells.Methods We treated human LAC A549 cells with isotonic physiological saline (control) and TMD at 3 μg/mL (low-dose TMD), 30 μg/mL (medium-dose TMD) and 300 μg/mL (high-dose TMD), respectively.After 48 hours of intervention, we detected the proliferation of the cells by CCK-8 assay, determined their apoptosis by Annexin-V FITC/PI double staining, measured the protein expressions of XIAP, Survivin, Bcl-2, Bax, and Caspase-3 in the cells by Western blot, and examined the cell cycle by FCM.Results Compared with the control group, tramadol treatment significantly reduced the absorbance value of the LAC A549 cells (P<0.05) and elevated the level of their apoptosis in the low-, medium- and high-dose TMD groups ([2.1±0.3]% vs [4.9±0.7]%, [9.4±1.4]% and [19.2±2.4]%, P<0.05), both in a dose-dependent manner. In comparison with the saline control, high-dose TMD group showed markedly down-regulated expressions of Survivin (0.98±0.04 vs 0.31±0.02, P<0.05) and XIAP (0.99±0.02 vs 0.38±0.04, P<0.05) but up-regulated expression of Caspase-3 (0.97±0.03 vs 1.06±0.03, P<0.05) in the LAC A549 cells. The ratio of G0/G1 cells was remarkably decreased while those of S and G2/M cells significantly increased, all in a dose-dependent manner (P<0.05).Conclusion Tramadol can inhibit the proliferation, promote the apoptosis and block the cycle of human LAC A549 cells, which may be associated with its abilities of down-regulating the expressions of Survivin and XIAP and promoting the activation of Caspase-3 in the cells.