索拉非尼联合溶瘤痘苗病毒对肝癌细胞抑制作用及其机制探讨（英文）  

Synergistic anti-tumor effects of oncolytic virus therapy combined with sorafenib on human hepatocellular carcinoma

作　　者：李亚姣 雷文 秦云 应畅[1] 周秀梅[1] 

机构地区：[1]浙江理工大学生命科学学院新元医学与生物技术研究所,杭州310018 [2]浙江大学医学院第一附属医院,杭州310003

出　　处：《华中师范大学学报（自然科学版）》2017年第5期638-645,共8页Journal of Central China Normal University：Natural Sciences

基　　金：国家自然科学基金青年科学基金项目(81602706);国家自然科学基金项目(81172137);浙江省自然科学基金项目(LY13H080005);浙江省公益性技术应用研究计划项目(2015C37035);浙江省中医药科学研究基金项目(2017ZB006)

摘　　要：人类肝细胞癌是全球最常见和具有高致命性的癌症之一.中国的肝癌患者在全球居于首位,目前仍然没有找到有效的方法来治疗肝癌.近年,溶瘤痘病毒(vaccinia virus)由于其高效的抗癌效应,副反应较低和良好的安全性已成为一种癌症治疗的新方法,且已经广泛应用于癌症的治疗中.索拉非尼,一种新型的肿瘤激酶抑制剂,作为化疗药物可安全有效地治疗肝癌,且已应用于临床试验中.本实验将索拉非尼与溶瘤痘病毒联用并探究其在肝癌细胞中的抗肿瘤的效应.通过体外MTT,Hochest,流式细胞术,Western blot等细胞实验和体内小鼠移植瘤模型的建立以及免疫组化的分析,发现索拉非尼联合溶瘤痘病毒,可显著的抑制肿瘤细胞的生长,促进肿瘤细胞的凋亡.小鼠移植瘤模型结果表明,随着时间的延长,联合处理组的肿瘤大小有下降的趋势.联合使用索拉非尼和溶瘤痘病毒可能为一项肝癌治疗的新途径.Human hepatocellular carcinoma is one of the most common and high fatal cancer in the world. In China, the liver cancer rates is the highest in the world. Many researchers put into the research of liver cancer and tried many ways and methods, but still couldn＇t find effective ways to cure hepatocellular carcinoma. In the recent years, oncolytic vaccinia virus become a promising novel way in cancer treatment because of its efficient anti tumor effect, low side effects and good safety, and has been widely used in the treatment of cancer. Sorafenib, a new tumor-targeting kinase inhibitor, has shown its effective and safe chemotherapy drugs in treatment of HCC, and has already used in clinical trials. In the present study, we combined sorafenib with VV to explore its anti- tumor effects. Through in vitro experiments like MTT, Hoechst, Flow cytometry, Western blot and in vivo transplantation of tumor model and immunohistochemical analysis, it＇s demonstrated that combination of sorafenib and vaccinia virus significantly inhibited the growth of tumor cells and promoted apoptosis of tumor cells. According to the result of mice transplanted tumor model, the date showed that with the extension of time, the combined group tumor size has a tendency to decline. Thus, the combination use of sorafenib and vaccinia virus might be a novel approach for liver cancer therapy.

关 键 词：溶瘤痘病毒 索拉非尼 联合治疗 肝癌 

分 类 号：Q291[生物学—细胞生物学]