Targeted IL-24 gene therapy inhibits cancer recurrence after liver tumor resection by inducing tumor cell apoptosis in nude mice.
BACKGROUND
Interleukin-24 (IL-24) is a novel candidate tumor suppressor that induces tumor cell apoptosis experimentally in a variety of human malignant cells including liver cancer cells. The present study was conducted to investigate the potential effect of recombinant adeno-associated virus (rAAV)-mediated IL-24 gene therapy on tumor recurrence and metastasis by inducing tumor cell apoptosis in a hepatocellular carcinoma (HCC) model in nude mice.


METHODS
We established a recurrent and metastatic HCC model in nude mice and constructed an rAAV vector carrying alpha-fetoprotein (AFP) promoter for expressing the IL-24 gene (rAVV/AFP/IL-24). The vector was administered by regional injection (liver incisal margin). AFP was detected by radiation immunoassay. Histological evaluation of tumor recurrence and metastasis was performed for the liver and lung. The effect of tumor cell apoptosis was confirmed by TUNEL analysis.


RESULTS
IL-24 gene therapy prevented tumor recurrence and metastasis, as evidenced by marked decreases in the number of metastatic tumor nodules and tumor volume in the liver and lung. At the same time, serum AFP concentration decreased markedly in the IL-24 group compared with the control or rAAV groups (P<0.05). IL-24 gene therapy inhibited tumor recurrence and metastasis as evidenced by the induction of tumor cell apoptosis.


CONCLUSIONS
The results demonstrated that targeted IL-24 gene therapy was effective in the prevention of postoperative recurrence and metastasis in an HCC nude mice model by induction of tumor cells apoptosis with potential minimum tumor burden.
Yang
Yong-Jiu
YJ
Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
Chen
Da-Zhi
DZ
Li
Li-Xin
LX
Sheng
Qin-Song
QS
Jin
Zhong-Kui
ZK
Zhao
De-Fang
DF
D000818:Animals; D017209:Apoptosis; D000229:Dependovirus / Q000235:genetics; D015316:Genetic Therapy; D006498:Hepatectomy; D020287:In Situ Nick-End Labeling; D007378:Interleukins / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D011401:Promoter Regions, Genetic; D000509:alpha-Fetoproteins / Q000032:analysis / Q000235:genetics; D000099180:Interleukin-24
D007378:Interleukins; D000509:alpha-Fetoproteins; D000099180:Interleukin-24