mda-7/IL-24 induces apoptosis in human GBC-SD gallbladder carcinoma cells via mitochondrial apoptotic pathway.
mda-7/IL-24 has tumor-suppressor activity in a broad spectrum of human cancer cells. However, the therapeutic effect of the recombinant human IL-24 protein on human gallbladder carcinoma has rarely been explored. In this study, we used a human gallbladder carcinoma cell line (GBC-SD) to explore the effect of adenovirus-mediated IL-24 (Ad-IL24) gene therapy on GBC-SD cells. We show that Ad-IL24 treatment of GBC-SD cells in vitro conspicuously induced apoptosis of GBC-SD cells. We also demonstrate that the in vivo treatment of GBC tumor-bearing athymic nude mice intratumorally injected with Ad-IL24 significantly suppressed GBC growth. To further explore the mechanism that mda-7/IL-24 utilized in tumor cell apoptosis, we examined molecules and pathways involved in apoptotic regulation and found that Ad-IL24 induced the down-regulation of anti-apoptotic gene Bcl-2 and the release of cytochrome c, which subsequently activated caspase-9, caspase-3 and PARP to induce apoptosis. In summary, adenovirus (AdV)-mediated IL-24 overexpression exerted potent antitumor activity via stimulating mitochondrial apoptotic pathway in GBC-SD. Therefore, mda-7/IL-24 has the potential to serve as a tool for targeted gene therapy in the treatment of gallbladder cancer.
Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
Jianguang
J
Jia
Songgang
S
Li
Wei
W
Gong
Jing
J
Ding
Cuifu
C
Fang
Zhiwei
Z
Quan
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D019254:Genes, bcl-2; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D007378:Interleukins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023041:Xenograft Model Antitumor Assays; D000099180:Interleukin-24
D007378:Interleukins; D000099180:Interleukin-24