Antitumor activities of an oncolytic adenovirus equipped with a double siRNA targeting Ki67 and hTERT in renal cancer cells.
RNA interference has been proven to be a powerful tool for gene knockdown. Our previous study demonstrated that a Ki67 shRNA carried by an adenovirus reduced Ki67 expression. In this study, we constructed novel oncolytic adenoviruses in which the Ki67 core promoter drove expression of the E1A gene. These adenoviruses were equipped with either a Ki67 small interfering RNA (siRNA), a human telomerase reverse transcriptase (hTERT) siRNA or a double siRNA targeting Ki67 and hTERT. We identified the antitumor activities of oncolytic adenoviruses in 3 renal cancer cell lines, human normal renal tube cell HK-2 and also in nude mice bearing KETR-3-xenografted tumors. Our results showed that these oncolytic adenoviruses, especially Ki67-ZXC2-double siRNA, could effectively induce silencing of the Ki67 and hTERT genes, allow efficient viral replication and induce significant apoptosis of renal cancer cells in vitro and in nude mice. We concluded that a dual siRNA mediated by oncolytic virotherapy could be an effective strategy for cancer gene therapy.
Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou 221002, China.
Lin
L
Fang
Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou 221002, China.
Qian
Q
Cheng
Laboratory of Urology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Wang
W
Li
Laboratory of Urology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
Junjie
J
Liu
Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou 221002, China.
Liantao
L
Li
Department of Radiology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. Electronic address: zhangqifengfl@126.com.
Kai
K
Xu
Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou 221002, China; Laboratory of Urology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. Electronic address: fl@xzmc.edu.cn.
Junnian
J
Zheng
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003588:Cytopathogenic Effect, Viral; D004195:Disease Models, Animal; D015870:Gene Expression; D023061:Gene Order; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics*; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; C509186:TERT protein, human; D019098:Telomerase
Human telomerase reverse transcriptase; Ki67; RNA interference; Renal cell carcinoma (RCC)