盐酸阿霉素增强溶瘤腺病毒ZD55-TRAIL抑制肝癌细胞生长的研究  

Novel Synergistic Anti-tumor Effects of DOX with Oncolytic Adenovirus ZD55-TRAIL on Hepatocellular Carcinoma Cells

作　　者：刘涛[1] 韩华锋[1] 马步云[1] 杨远勤[1] 卓玲燕 周立[1] 王毅刚[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

出　　处：《中国生物工程杂志》2014年第2期26-33,共8页China Biotechnology

基　　金：国家自然科学基金(81272687);国家"863"计划(2012AA020806);浙江省自然科学基金(LZ13H160004)资助项目

摘　　要：盐酸阿霉素(DOX)作为一种抗肿瘤抗生素,通过抑制癌细胞遗传物质的合成,对多种肿瘤均有杀伤作用,然而,其单独作用疗效有限,且加大剂量时其副作用较强。目前,携带抗癌基因的溶瘤腺病毒在肿瘤治疗中的作用日渐显现,溶瘤腺病毒ZD55-Trail联合DOX治疗肝癌的研究鲜有报道。通过MTT和结晶紫染色试验检测DOX药物处理对肝癌细胞系Bel-7404存活率的变化情况;Hoechst33342染色和流式细胞术检测肝癌细胞的凋亡;Western blot检测Trail蛋白和凋亡相关蛋白的表达;免疫荧光和流式细胞术检测凋亡相关受体表达的情况。结果显示,ZD55-Trail与DOX联合使用能够有效抑制肝癌细胞增长并诱导其凋亡,并且联合处理能增加Trail受体DR4和DR5的表达。初步探讨了DOX与ZD55-Trail两者协同诱导肝癌细胞凋亡的机制,为利用ZD55-Trail与DOX联合治疗肝癌提供依据。Doxorubicin hydrochloride, an antitumor antibiotic, exhibits prominent killing effects in numerous malignant turnouts by suppressing the synthesis of genetic material of carcinoma cells. Nevertheless, the therapeutic effect with single drug is limited and the side-effect is very strong when the dose was added. The oncolytic adenovirus armed with cancer suppressor gene plays an important role in cancer therapy. However, there is little report for the treatment of liver cancers with the combination of oncolytic adenovirus ZD55 armed with Trail and doxorubiein hydrochloride. MTF assay and crystal violet assay were used to determine the growth inhibition effects of various treatments in hepatoma carcinoma cell Bel-7404; and Hoechst 33342 staining and flow cytometry assay were used to evaluate the cell apoptosis; with Western blotting assay to detect the trail and apoptosis-related protein expression; with immunofluorescence method and flow cytometry assay to detect the expression of apoptosis-related receptor. The results indicate that the combination therapy of oncolytic adenovirus ZD55 armed with Trail and doxorubicin hydrochloride could more significantly inhibited tumor cell proliferation and induce cell apoptosis compared with single drug. The cooperation mechanism of the two drugs refer to the expression level of the Trail receptor DR4 and DR5 was explored. The above primarily explored the mechanism of apoptotic inducement by the synergy treatments with DOX and ZD55-Trail, which provide the basis for further combinational treatment of hepatocellular carcinoma.

关 键 词：肝癌 凋亡 

分 类 号：Q789[生物学—分子生物学]