携带小鼠白介素12基因的增殖型腺病毒对胃癌细胞株化疗敏感性影响的研究

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

Effect of replication-competent adenovirus-mediated interleukin-12 gene to chemotherapeutic sensitivity on gastric cancer cell

OBJECTIVE: To investigate the effect of replication-competent adenovirus-mediated interleukin-12 gene to chemotherapeutic sensitivity on gastric cancer cell. METHODS: Replication-competent adenovirus and replication-competent adenovirus- mediated interleukin- 12 gene was constructed and expanded separately. The mortality of gastric cancer cell caused by the CNHK200- mIL- 12, Onyx- 015 in combination with different dosages of chemotherapeutic agents were evaluated by MTT assay at the same viral titer with a series of different dosages of chemotherapeutic agent,or at a series of different viral titers with the same dosage of chemotherapeutic agent. The curative effect to the xenografts gastric tumor in nude mouse was also observed by two viruses solely or together with 5-Fu. RESULTS: The lytic activity of replication-competent adenovirus to gastric cancer cell line SGC-7901 was relatively poor at MOI value of 0.5, but it could be improved significantly when combined with chemotherapeutic agents of ADM, 5-Fu or CAP compared to the simple chemical therapy (P< 0.05). Chemotherapeutic agent 5- Fu could not effectively kill SGC-7901 when used at a relatively low dosage of 10microg/ml,whereas its activity could be improved when combined with a replication-competent adenovirus,and the killing rate was much higher than that with replication-competent adenovirus solely (P< 0.05). The gastric tumor xenografts was prevented and killed by replication adenovirus solely or combined with 5-Fu. CONCLUSION: The replication- competent adenovirus- mediated interleukin- 12 gene can increase the chemotherapeutic sensitivity on gastric cancer cell. There is syneratic effect between the replication adenovirus and the chemotherapeutic agents in killing gastric cancer cell.