吉西他滨增强HUVEC疫苗抗胰腺癌作用实验研究

Experimental study of enhanced anti-pancreatic cancer effects by combination treatment with HUVEC vaccine and gemcitabine

目的研究低剂量化疗药吉西他滨(gemcitabine,GEM)能否增强人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)疫苗抗胰腺癌作用,并探讨其作用机制。方法以Pan02小鼠胰腺癌细胞接种C57BL/6小鼠,建立皮下移植瘤模型,动物随机分为PBS组、GEM组、HUVEC组、HUVEC-GEM组,观察各组小鼠肿瘤生长及不良反应情况。通过小鼠免疫血清中HUVEC抗体检测实验、脾淋巴细胞增殖实验、细胞毒性T淋巴细胞杀伤实验及INF-γ测定实验确定GEM能否增强HUVEC疫苗诱导的免疫应答。结果皮下移植瘤实验结果表明GEM引入HUVEC疫苗免疫方案后可以增强疫苗治疗性抗胰腺癌作用;酶联免疫实验结果证实GEM可以有效提升疫苗治疗组小鼠免疫血清中的HUVEC抗体及IFN-γ水平;脾淋巴细胞增殖实验及CTL杀伤结论低剂量GEM可以增强HUVEC疫苗诱导的免疫应答水平从而提升HUVEC疫苗的抗胰腺癌作用。

Aim To investigate whether low dose gemcitabine(GEM)could enhance the anti-pancreatic cancer effects of human umbilical vein endothelial cell(HUVEC)vaccine.Methods C57BL/6 mice were randomly divided into four groups:PBS control group,GEM group,HUVEC vaccine group and HUVEC vaccine combined GEM group(HUVEC-GEM group).Mice were inoculated with Pan02 pancreatic cancer cells to establish a subcutaneous xenograft model to observe tumor growth and adverse reactions in tumor bearing mice.Whether GEM could enhance the immune responses induced by HUVEC vaccine was determined by ELISA analysis of the immune serum,splenic lymphocyte proliferation assay,cytotoxic T lymphocyte killing assay and IFN-γcontent assay.Results The results of subcutaneous transplantation tumor model showed that the introduction of GEM into the HUVEC vaccine treatment could enhance the therapeutic anti-pancreatic cancer effects of HUVEC vaccine.Enzyme-linked immunoassay results confirmed that GEM acted as an immune adjuvant could effectively increase the HUVEC antibodies and IFN-γlevel in the immune serum of mice.The results of lymphocyte proliferation experiment and CTL killing activity assay indicated that GEM could effectively enhance the spleen lymphocyte transformation activity and CTL killing ability of HUVEC vaccine immunized mice.Conclusions Low dose GEM could enhance the immune responses induced by HUVEC vaccine and thus enhance the anti-Pan02 pancreatic cancer effects of HUVEC vaccine.