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目的研究携带白介素12(mIL-12)基因的增殖型腺病毒CNHK200-mIL-12对胃癌细胞株化疗敏感性的影响。方法扩增增殖型腺病毒Onyx-015及携带小鼠mIL-12基因的增殖型腺病毒CNHK200-mIL-12,利用MTT法测定同一病毒滴度下联合应用不同浓度化疗药物及同一化疗药物浓度下联合应用不同滴度病毒对胃癌细胞株杀伤作用,并观察增殖型腺病毒联合化疗药物对裸鼠腹腔种植瘤的抑制作用。结果当不同感染复数(MOI)=0.5时,增殖型病毒Onyx-015、CNHK200-mIL-12对胃癌细胞SGC-7901无明显的杀伤作用。加入化疗药物阿霉素(ADM)、氟尿嘧啶(5-Fu)和卡铂(CAP)后,两者对SGC-7901的杀伤率随着药物浓度增加都有不同程度的升高,与单纯使用化疗药物组比较,差异有统计学意义(P<0.05)。浓度为10μg/ml的5-Fu对SGC-7901的杀伤作用不明显,单用增殖型腺病毒对SGC-7901的杀伤作用也较弱,两者联合应用杀伤活性明显提高,与未加5-Fu组比较,差异有统计学意义(P<0.05)。动物试验证明:经Onyx-015联合5-Fu治疗后,裸鼠腹腔内肿瘤形成率为1/6,而CNHK200-mIL-12联合5-Fu组未见腹腔内肿瘤生长,与单用增殖型腺病毒或单用化疗者比较,差异有统计学意义(P<0.05)。结论携带mIL-12基因的增殖型腺病毒能够提高胃癌细胞株对化疗药物的敏感性,在杀伤胃癌细胞株的作用中
Objective To investigate the effect of CNHK200-mIL-12, a proliferating adenovirus carrying interleukin 12 (mIL-12), on the chemosensitivity of gastric cancer cell lines. Methods The proliferating adenovirus Onyx-015 and the proliferating adenovirus CNHK200-mIL-12 carrying murine mIL-12 gene were amplified by MTT assay. The titer was determined by MTT assay with different concentrations of chemotherapeutic agents and the same concentration of chemotherapeutic agents Combined application of different titer of virus on gastric cancer cell killing, and observe the proliferation of adenovirus combined with chemotherapy drugs on nude mice peritoneal tumor growth inhibition. Results The proliferative viruses Onyx-015 and CNHK200-mIL-12 had no obvious killing effect on SGC-7901 cells at different MOI values of 0.5. The killing rates of SGC-7901 and SGC-7901 increased with the increase of drug concentration after adding chemotherapeutic drugs ADM, 5-Fu and CAP. Compared with the chemotherapy alone Compared with the drug group, the difference was statistically significant (P <0.05). The killing effect of 5-Fu with 10μg / ml on SGC-7901 was insignificant. The cytotoxicity of SGC-7901 with adenovirus alone was also weaker than that of SGC-7901. Fu group, the difference was statistically significant (P <0.05). Animal experiments show that: Onyx-015 combined with 5-Fu treatment, intraperitoneal tumor formation rate of 1/6 in nude mice, and CNHK200-mIL-12 combined with 5-Fu group no intra-abdominal tumor growth, and single proliferative Adenovirus or chemotherapy alone, the difference was statistically significant (P <0.05). Conclusion The adenovirus carrying mIL-12 gene enhances the sensitivity of gastric cancer cell lines to chemotherapeutic drugs. In the role of killing gastric cancer cell lines