Inhibition of renal cancer cell growth in vitro and in vivo with oncolytic adenovirus armed short hairpin RNA targeting Ki-67 encoding mRNA.
RNA interference (RNAi) has been proved to be a powerful tool for gene knockdown purpose and holds great promise for the treatment of cancer. Our previous study demonstrated that the reduction of Ki-67 expression by means of chemically synthesized siRNAs and shRNAs expressed from plasmid resulted in proliferation inhibition in human renal carcinoma cells. In this study, we constructed a novel oncolytic adenovirus-based shRNA expression system, ZD55-Ki67, and explored ZD55-Ki67-mediated RNAi for Ki-67 gene silencing. Our results showed that ZD55-Ki67 could induce silencing of the Ki-67 gene effectively, allow for efficient tumor-specific viral replication and induce the apoptosis of tumor cells effectively in vitro and in nude mice. We conclude that combining shRNA gene therapy and oncolytic virotherapy can enhance antitumor efficacy as a result of synergism between CRAd oncolysis and shRNA antitumor responses.
Zheng
J-N
JN
Laboratory of Urology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China. jnzheng@xzmc.edu.cn
Pei
D-S
DS
Mao
L-J
LJ
Liu
X-Y
XY
Mei
D-D
DD
Zhang
B-F
BF
Shi
Z
Z
Wen
R-M
RM
Sun
X-Q
XQ
D000256:Adenoviridae; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques / Q000379:methods; D015316:Genetic Therapy; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses; D034622:RNA Interference; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D034741:RNA, Small Interfering