中国肿瘤生物治疗杂志2017，Vol.24Issue(5)：472-477,6.DOI:10.3872/j.issn.1007-385X.2017.05.003
表达mIL-21的溶瘤痘苗病毒对小鼠乳腺癌的治疗作用
Therapeutic effect of the oncolytic vaccinia viruses with expression of mIL-21 on breast cancer of mouse
摘要
Abstract
Objective:To evaluate the in vitro and in vivo efficacy of tumor-targeted oncolytic vaccinia virus (VV) vectors,VV△TK△N1L-RFP and VV△TK△N1L-mIL-21,on murine breast cancer cell lines (JC,TUBO and 4T1).Methods:The cytotoxicity of the viruses (VV△TK△N1L-RFP and VV△TK△N1L-mIL-21) at different mass concentrations on JC,TUBO and 4T1 cells was compared by MTT assay.The replication ability of the two viruses in the three cell lines was tested by TCID50.ELISA assay was performed to detect mIL-21 expression in the supernatants of the culture medium of three cell lines after virus infection.Orthotopic models of triple negative breast cancer (4T1) and Her-2 amplified breast cancer (TUBO) in the BALB/c mice were established to investigate the antitumor efficacy of the two VVs.Results:The two viruses were all able to replicate in breast cancer JC,TUBO and 4T1 cell lines,and low dose of VV caused significant cytotoxicity against breast cancer cell lines.High level of mIL-21 protein was detected in the cell culture supernatants after VV△TK△N1L-mIL-21 infection.In the orthotopic 4T1 breast cancer model,the viruses did not show significant anti-tumor effect (P ＞ 0.05);however,in the orthotopic TUBO breast cancer model,tumor growth was significantly inhibited by both viruses (P ＜0.05,P ＜0.01),and the survival time(P ＜0.01) of tumor bearing mouse was prolonged in both VV△TK△N1L-RFP and VV△TK△N1L-mIL-21 treatment group.Conclusion:Both VV△TK△N1L-RFP and VV△TK△N1L-mIL-21 viruses could specifically replicate and showed cell killing effect on breast cancer cells.The two viruses have different in vivo therapeutic effects on Her-2 gene amplified breast cancer and triple negative breast cancer.关键词
痘苗病毒/乳腺癌/白细胞介素-21Key words
vaccinia virus(VV)/breast cancer/IL-21分类
医药卫生引用本文复制引用
刘超,王继伟,王鹏举,张忠献,褚永超,吕鹏威,谷元廷,王尧河..表达mIL-21的溶瘤痘苗病毒对小鼠乳腺癌的治疗作用[J].中国肿瘤生物治疗杂志,2017,24(5):472-477,6.基金项目
国家自然科学基金资助项目(No.81272525,No.81201792).Project supported by the Nature Sciences Foundation of China (No.81272525,No.81201792) （No.81272525,No.81201792）
