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目的评价化疗药物紫杉醇联合应用肿瘤疫苗对小鼠Lewis肺癌皮下移植瘤的治疗效果。方法以编码有GM-CSF的腺病毒感染Lewis肺癌细胞3LL,制备肿瘤疫苗3LL/GM-CSF。以2×104个3LL瘤细胞皮下注射C57BL/6(H-2b)小鼠腹股沟部,制备小鼠皮下移植瘤。检测体内、外应用紫杉醇对Lewis肺癌细胞3LL的杀伤敏感性。在小鼠Lewis肺癌皮下移植瘤体内首先以紫杉醇化疗,随后以肿瘤疫苗3LL/GM-CSF免疫;或反之,首先以肿瘤疫苗免疫,随后以紫杉醇化疗,观察肿瘤生长和小鼠生存状况,以及检测小鼠体内对肿瘤的特异性杀伤效率和免疫应答记忆反应。结果紫杉醇体外作用于3LL肿瘤细胞,24h后在浓度为100nmol/L时可使32.10%的3LL肿瘤细胞发生死亡;但体内注射紫杉醇(5、10和25mg/kg)不能使所有3LL荷瘤小鼠肿瘤消退。体内使用紫杉醇后应用3LL/GM-CSF肿瘤疫苗,70%的荷瘤小鼠发生显著的肿瘤消退,与单纯化疗的小鼠相比生存时间明显延长(70.0vs27.5d);化疗后应用肿瘤疫苗诱导了体内对3LL的特异性杀伤,第3天体内杀伤率达41.35%;同时,存活小鼠能抵抗2×1043LL肿瘤细胞的再次攻击。接种3LL/GM-CSF肿瘤疫苗后应用紫杉醇化疗却不能使肿瘤消退。结论化疗后应用肿瘤疫苗免疫可诱导出抗原特异性免疫效应,使荷瘤小鼠肿瘤消退并延长生存时间,为临床开展化疗后的肿瘤疫苗主动免疫提供了实验依据。
Objective To evaluate the therapeutic effect of paclitaxel combined with tumor vaccine on subcutaneous xenografts of Lewis lung carcinoma in mice. Methods Lewis lung cancer cells 3LL were infected with adenovirus encoding GM-CSF, and tumor vaccine 3LL / GM-CSF was prepared. Subcutaneous xenografts of mice were prepared by subcutaneous injection of the inguinal portion of C57BL / 6 (H-2b) mice into 2 × 10 4 3LL tumor cells. To detect the in vitro and in vivo effects of paclitaxel on Lewis lung carcinoma cells 3LL killing sensitivity. In mice bearing Lewis lung cancer subcutaneously transplanted with paclitaxel, they were first immunized with the tumor vaccine 3LL / GM-CSF or, conversely, immunized with the tumor vaccine followed by paclitaxel chemotherapy to observe tumor growth and mouse survival as well as detection Mice specific tumor killing efficiency and immune response to memory response. Results paclitaxel in vitro effects on 3LL tumor cells, 32.10% of the 3LL tumor cells died after 24 hours at a concentration of 100nmol / L; but in vivo injection of paclitaxel (5,10 and 25mg / kg) can not make all 3LL tumor-bearing mice Tumor regression. After in vivo administration of paclitaxel 3LL / GM-CSF tumor vaccine, 70% of tumor-bearing mice developed significant tumor regression, compared with chemotherapy alone mice significantly prolonged survival time (70.0vs27.5d); application of tumor vaccine after chemotherapy Induced the specific killing of 3LL in vivo. The killing rate in vivo was 41.35% on the third day. At the same time, the surviving mice were able to resist the re-attack of 2 × 1043LL tumor cells. Chemotherapy with paclitaxel after inoculation of the 3LL / GM-CSF tumor vaccine failed to regress the tumor. Conclusion The application of tumor vaccine after chemotherapy can induce antigen-specific immune response, tumor regression in tumor-bearing mice and prolongation of survival time, which provides an experimental basis for the active immunization of tumor vaccine after chemotherapy.