Synergistic effect of oxymatrine and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cells

AIM:To investigate the synergistic effect of oxymatrine (OM) and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cell lines SGC-7901, MKN-45, MKN-74. METHODS:Human gastric cancer lines SGC-7901, MKN-45, MKN-74 were treated with OM in the absence and presence of NM-3.The inhibitory rates were detected by MTT assay.Synergistic effect of OM and NM-3 on the growth of survivin, bcl-2, bax and p 53 in SGC-7901 cells were examined by semiquantitative RT-PCR and Western blotting, and their growth inhibitory effects were also observed on SGC-7901 tumor xenograft in nude mice. RESULTS: O M c o m b i n e d w i t h N M -3 e x h i b i t e d asynergistic inhibitory effect on the growth of SGC-7901, MKN-45 and MKN-74 cells in a time-dependent manner.Twenty-four hours after treatment with OM, NM-3 alone and their combination, mRNA expression of survivin and bcl-2 in SGC-7901 cells decreased, p 53 mRNA expression increased.OM (4 g/L) combined with NM-3 significantly increased the expression of p 53 mRNA and decreased the expression of survivin and bcl-2 compared with either agent alone (193% ± 34% vs 129% ± 12%; 44% ± 18% vs 92% ± 18%; 36 ± 17% vs 93% ± 23%, P < 0.05).Western blotting showed that the synergistic effect of OM and NM-3 on protein translation of survivin, bcl-2 and p 53 was in accordance with their mRNAs.Furthermore, OM/NM-3 combination obviously exhibited antitumor growth effect in xenografted human gastric cancer cells SGC-7901 compared with either agent alone.CONCLUSION: OM combined with NM-3 has synergistic inhibitory effects on human gastric cancer cells in vitro and can suppress the growth of xenografted human gastric cancer cells SGC-7901 in vivo .