摘要
背景:肿瘤坏死因子-α(TNF-α)是抗肿瘤活性很强的细胞因子,但较多的全身毒副作用限制了其应用。目前发现小剂量TNF-α联合化疗药物可提高化疗效果。目的:探讨TNF-α联合阿霉素(ADM)对人胃癌细胞株SGC-7901的治疗作用及其机制。方法:体外常规培养人胃癌细胞株SGC-7901,并分为ADM组(64、16、4、1、0.25μg/mL)、TNF-α组(16 000、4000、1000、250、62.5 IU/mL)、联合组(ADM 5μg/mL+TNF-α4000 IU/mL)、阴性对照组和空白对照组。以MTT法观察细胞生长,流式细胞术检测细胞周期和凋亡,蛋白质印迹法检测caspase-8蛋白表达。构建裸鼠胃癌移植瘤模型,分为阴性对照组、ADM组(2 mg/kg)和联合组(ADM 2 mg/kg+TNF-α5×104IU/kg),观察肿瘤生长情况。结果:与ADM组相比,联合组SGC-7901细胞存活率明显降低,S期和G2期细胞比例、细胞凋亡率、caspase-8蛋白表达均明显升高;体内实验亦显示联合组对裸鼠移植瘤的抑瘤率明显高于ADM组。结论:TNF-α与ADM联合应用可增加化疗药物对胃癌细胞的杀伤作用,其机制部分与促进细胞凋亡和改变细胞周期有关。
Background： Tumor necrosis faetor-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 easpase-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.
出处
《胃肠病学》
2012年第10期609-613,共5页
Chinese Journal of Gastroenterology
