Synergistic antitumor effect of TRAIL and IL-24 with complete eradication of hepatoma in the CTGVT-DG strategy.
The ZD55-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and ZD55-interleukin (IL)-24 were constructed by inserting TRAIL or IL-24 gene separately into the oncolytic adenovirus named ZD55 (with adenovirus E1B-55kD deletion). The resulting ZD55-TRAIL and ZD55-IL-24 were used in combination to treat xenograft tumors in nude mice model. The results showed that it can not only completely eliminate BEL7404 hepatoma xenograft but also have excellent antitumor effect against gaster, lung, prostate, and breast carcinomas. It was also found that ZD55-TRAIL could not only suppress the tumor growth promoting effect by ZD55-IL-24 at lower dosage, but also substantially reduce the cancer cell viability in their combined use. This is because ZD55-IL-24 and ZD55-TRAIL could mutually enhance each other's antitumor effect greatly. All these findings conspicuously showed the synergistic antitumor effect of TRAIL and IL-24, which is also the reason for the antitumor effect by the combined use of TRAIL and IL-24 in vitro and also in vivo.
State Key Laboratory of Cell Biology,  Institute of Biochemistry and Cell Biology,  Shanghai Institutes for Biological Sciences,  Chinese Academy of Sciences, Shanghai 200031,  China.
Ying
Y
Cai
Xinran
X
Liu
Weidan
W
Huang
Kangjian
K
Zhang
Xin-yuan
XY
Liu
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004357:Drug Synergism; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D007378:Interleukins / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D050130:Oncolytic Virotherapy / Q000379:methods*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
D000970:Antineoplastic Agents; D007378:Interleukins; D053221:TNF-Related Apoptosis-Inducing Ligand; D000099180:Interleukin-24