Synergistic Effect and Mechanism of TNF-α Combined with Adriamycin on Human Gastric Cancer Cell Line SGC-7901

Background: Tumor necrosis factor-α(TNF-α) is an anti-tumor cytokine,but the systemic toxicity limits its use.However,studies have shown that low dose TNF-α combined with chemotherapeutic drug can enhance therapeutic effect.Aims: To investigate the synergistic effect and mechanism of TNF-α combined with adriamycin(ADM) on human gastric cancer cell line SGC-7901.Methods: Human gastric cancer cell line SGC-7901 was conventionally cultured in vitro,and was divided into ADM groups(64,16,4,1,0.25 μg / mL),TNF-α groups(16 000,4000,1000,250,62.5 IU / mL),combined group(ADM 5 μg / mL + TNF-α 4000 IU / mL),negative control group and blank control group.MTT assay was used to observe cell growth;cell cycle and apoptosis was determined by flow cytometry;protein expression of caspase-8 was detected by Western blotting.Gastric cancer xenograft model was established in nude mice,and were divided into negative control group,ADM group(2 mg / kg) and combined group(ADM 2 mg / kg + TNF-α 5 × 10 4 IU / kg);tumor growth was observed.Results: Compared with ADM group,survival rate of SGC-7901 cells was significantly decreased,and the ratio of cells in S phase and G2 phase,cell apoptosis and protein expression of caspase-8 were significantly increased in combined group.Inhibition rate of transplantation tumor in nude mice in combined group was significantly higher than that in ADM group in vivo.Conclusions: TNF-α combined with ADM can enhance the lethal effect of chemotherapeutic drug on gastric cancer cells,its mechanism may be partly related to the enhanced cell apoptosis and change of cell cycle.