Oncolytic adenovirus mediated Survivin RNA interference and 5-fluorouracil synergistically suppress the lymphatic metastasis of colorectal cancer.
Colorectal cancer is one of the leading malignancies in the world. The mortality is mainly caused by tumor metastasis. It is urgent to find new therapeutics against metastatic colorectal cancer. We constructed an adenovirus carrying a Survivin targeted shRNA, tested its effects alone or with 5-fluorouracil (5-FU) both in vitro and in a nude mouse xenograft model. Results showed that the recombinant adenovirus reduced the expression of Survivin effectively, and administration of virus together with 5-FU inhibited cancer cell metastasis both in vitro and in vivo at concentrations at which each agent alone was ineffective. We conclude Survivin targeted virotherapy together with 5-FU chemotherapy may be a promising treatment for metastatic colorectal cancer.
Shen
Wei
W
Department of General Surgery, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, PR China.
Tu
Jing-Kai
JK
Wang
Xue-Hu
XH
Fu
Zhong-Xue
ZX
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000628:therapy* / Q000821:virology; D000256:Adenoviridae / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000628:therapy* / Q000821:virology; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008207:Lymphatic Metastasis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000235:genetics*; D050130:Oncolytic Virotherapy / Q000379:methods*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D000077022:Survivin; D023041:Xenograft Model Antitumor Assays
D000964:Antimetabolites, Antineoplastic; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000077022:Survivin; D005472:Fluorouracil