摘要
【目的】探讨六味地黄丸对小鼠移植性肝癌HSVt-k/GCV自杀基因治疗增效作用的病理学机制。【方法】昆明种小鼠90只,随机分为5组:正常对照组、模型对照组、六味地黄丸治疗组(剂量为10 g.kg-1.d-1)、自杀基因治疗组(腹腔注射丙氧鸟苷100 mg.kg-1.d-1)、联合治疗组;选用H22与H22/tk细胞株皮下接种建立小鼠荷肝癌模型,以自杀基因疗法联合六味地黄丸进行治疗并观察疗效;对肿瘤组织进行病理学观察和半定量分析;采用免疫组化技术及原位末端标记(TUNEL)技术观察肿瘤细胞增殖核抗原(PCNA)的表达及凋亡情况。【结果】HSVt-k/GCV自杀基因系统联合六味地黄丸治疗较单独应用HSVt-k/GCV系统或六味地黄丸能更显著地抑制肿瘤生长;免疫组化及凋亡TUNEL染色结果表明联合治疗组对肿瘤细胞增殖的抑制及对肿瘤细胞凋亡的诱导作用与模型对照组比较,差异均有显著性意义(P<0.05)。【结论】六味地黄丸对实验性肝癌的自杀基因治疗具有增效作用,其机制可能与六味地黄丸抑制了自杀基因治疗过程中肿瘤细胞的加速增殖有关,也与协同促进自杀基因治疗诱导的肿瘤细胞凋亡有关。
[ Objective ] To explore the pathological mechanism of Liuwei Dihuang Bolus （LDB） on enhancing the effect of HSV-tk/GCV suicide gene therapy for mice transplanted hepatocarcinoma. [ Methods ] Ninety Kunming mice were randomized into 5 groups： normal control group, model group, LDB group （10g·kg^-1^d^-1）, suicide gene therapy group （intraperitoneal injection of guanosine ganciclovior） and the combined group. The transplanted tumor mice model of H22 hepatocarcinoma was established by subcutaneous inoculation of H22 and H22/tk cells. After treatment, the therapeutic effect in different groups was evaluated. The pathological changes of the tumor mass were observed and analyzed by semi-quantitative analysis. The expression of proliferating cell nuclear antigen （PCNA） and apoptosis of tumor cells were detected with immunohistochemical method and TUNEL technique. [ Results] HSV-tk/GCV suicide gene therapy combined with LDB had a better inhibitory effect on tumor growth than gene therapy or LDB only. The results of immunohistochemical method and TUNEL technique showed that the effect on inhibiting tumor cells proliferation and inducing tumor cells apoptosis in the combined group was better than that in the model group （ P 〈 01 05 ）. [ Conclusion ] LDB enhances the effect of HSV-tk/GCV suicide gene therapy for mice transplanted hepatocarcinoma, and its therapeutic mechanism may be related not only with the acceleration of tumor cells proliferation, but also with the enhancement of tumor cells apoptosis during suicide gene treatment.
出处
《广州中医药大学学报》
CAS
2007年第5期386-391,共6页
Journal of Guangzhou University of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(编号:30171201)
广州市科技计划项目(编号:2002J1-C7041)
广东省中医药管理局基金资助项目(编号:A401028)
