溶瘤腺病毒
Wnt信号通路
溶瘤病毒
癌症研究
癌症干细胞
转移
自噬
癌细胞
生物
干细胞
肝癌
癌症
细胞凋亡
信号转导
肝细胞癌
细胞生物学
肿瘤细胞
生物化学
遗传学
作者
Jian Zhang,Weijie Lai,Qiang Li,Yu Ye,Jin Jin,Wan Guo,Xiumei Zhou,Xinyuan Liu,Yigang Wang
标识
DOI:10.1016/j.bbrc.2017.07.041
摘要
Cancer stem cells (CSCs), which are highly differentiated and self-renewing, play an important role in the occurrence, therapeutic resistant and metastasis of hepatacellular carcinoma (HCC). Oncolytic adenoviruses have targeted killing effect on tumor cells, and are invoked as candidate drugs for cancer treatment. We designed a dual-regulated oncolytic adenovirus Ad.wnt-E1A(△24bp)-TSLC1 that targets Wnt and Rb signaling pathways respectively, and carries the tumor suppressor gene, TSLC1. Previous studies have demonstrated that oncolytic adenovirus mediated TSLC1can target liver cancer and exhibit significant cytotoxicity. However, whether Ad.wnt-E1A(△24bp)-TSLC1 can effectively eliminate liver CSCs remains to be explored. We first used the spheroid culture to enrich the liver CSCs-like cells, and detected the self-renewal capacity, differentiation, drug resistance and tumorigenicity. The results showed that Ad-wnt-E1A(△24bp)-TSLC1 could effectively lead to autophagic death. In addition, recombinant adenovirus effectively induced the apoptosis, inhibit metastasis of hepatic CSCs-like cells in vivo. Further animal experiments indicated that Ad-wnt-E1A(△24bp)-TSLC1could effectively inhibit the growth of transplanted tumor of hepatic CSCs and prolong the survival time of mice. Therefore, the novel oncolytic adenovirus Ad.wnt-E1A(△24bp)-TSLC1 has potential application as a therapeutic target for HCC stem cells.
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