mda-7/IL-24 induces apoptosis in human GBC-SD gallbladder carcinoma cells via mitochondrial apoptotic pathway
Jianguang Jia1, Songgang Li, Wei Gong
1Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
Abstract:
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.
Insights
Adenovirus-mediated interleukin-24 (Ad-IL24) gene therapy effectively triggered cancer cell death and suppressed tumor growth in gallbladder carcinoma models. This approach shows promise for targeted gallbladder cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Interleukin-24 (IL-24), also known as mda-7, exhibits broad-spectrum tumor-suppressor activity.
- The therapeutic potential of IL-24 for human gallbladder carcinoma remains largely unexplored.
Purpose of the Study:
- To investigate the efficacy of adenovirus-mediated IL-24 (Ad-IL24) gene therapy against human gallbladder carcinoma.
- To elucidate the molecular mechanisms underlying Ad-IL24-induced apoptosis in gallbladder cancer cells.
Main Methods:
- Utilized a human gallbladder carcinoma cell line (GBC-SD) for in vitro studies.
- Administered Ad-IL24 intratumorally in GBC tumor-bearing athymic nude mice for in vivo evaluation.
- Analyzed apoptosis-related molecules including Bcl-2, cytochrome c, caspases, and PARP.
Main Results:
- Ad-IL24 treatment induced significant apoptosis in GBC-SD cells in vitro.
- In vivo administration of Ad-IL24 markedly suppressed gallbladder tumor growth in mice.
- Ad-IL24 mediated apoptosis through down-regulation of Bcl-2, cytochrome c release, and activation of the caspase cascade.
Conclusions:
- Adenovirus-mediated IL-24 overexpression demonstrates potent antitumor activity against gallbladder carcinoma by activating the mitochondrial apoptotic pathway.
- IL-24 holds potential as a therapeutic agent for targeted gene therapy in gallbladder cancer treatment.
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