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[Adenovirus mediated IL-24 gene expression suppresses gastric cancer cell growth in vitro]
Wanrong Bao1, Jingcheng Miao, Weihua Sheng
1Department of Celluar and Molecular Biology, Medical School, Soochow University, Suzhou 215123, China.
Abstract:
To study the inhibitory effect of a recombinant adenoviral vector carrying human IL-24 gene on SGC-7901 human gastric cancer cell. We infected the SGC-7901 gastric cancer cells with Ad blank adenovirus at various multiplicity of infection (MOIs) to find the optimal infective dose. The SGC-7901 tumor cells were infected with Ad-IL-24 at the optimal MOI in the following experiments. Adenovirus-mediated IL-24 transcription expression in SGC-7901 cells was examined by RT-PCR. The growth-suppressing effect of Ad-IL-24 on SGC-7901 tumor cells was assessed by MTT assay. Apoptosis and cell cycle of SGC-7901 tumor cells infected with Ad-IL-24 was evaluated by flow cytometer (FCM), respectively. The karyomorphology of apoptotic SGC-7901 tumor cells was examined using Hoechst33258 staining under fluorescence microscopy. The expression of apoptosis-related genes was future determined by semi-quantification RT-PCR; We demonstrated that the MOI of 100 was the optimal infective dose in the study on adenovirus-mediated IL-24 gene transfer into SGC-7901 gastric cancer cell; IL-24 gene mediated by adenovirus could successfully transcribe in SGC-7901 tumor cells; Ad-IL-24 could significantly inhibit SGC-7901 tumor cell growth and induce apoptosis, it also can up-regulate the express of bax, caspase-3 and p53 whilst down-regulate the bcl-2 expression. Thus, adenovirus-mediated IL-24 expression had marked anti-tumor effect in suppressing SGC-7901 human gastric cancer cell growth and inducing apoptosis, which may be closely associated with its up-regulation of bax/bcl-2, caspase-3 and p53.
Insights
Adenovirus-mediated delivery of the human IL-24 gene effectively inhibits human gastric cancer cell growth. This gene therapy approach induces apoptosis and alters key gene expressions, showing significant anti-tumor potential.
Area of Science:
- Oncolytic Virotherapy
- Molecular Oncology
- Gene Therapy
Context:
- Gastric cancer remains a significant global health challenge with limited effective treatments.
- Adenoviral vectors offer a promising platform for targeted gene delivery in cancer therapy.
- Understanding the molecular mechanisms of IL-24 in gastric cancer is crucial for developing novel therapeutic strategies.
Purpose:
- To investigate the anti-tumor efficacy of a recombinant adenoviral vector carrying the human IL-24 gene (Ad-IL-24) against SGC-7901 human gastric cancer cells.
- To determine the optimal multiplicity of infection (MOI) for Ad-IL-24 transduction in SGC-7901 cells.
- To elucidate the effects of Ad-IL-24 on cell growth, apoptosis, cell cycle, and the expression of apoptosis-related genes.
Summary:
- The study identified an optimal MOI of 100 for Ad-IL-24 in SGC-7901 cells, confirming successful adenovirus-mediated IL-24 gene transcription.
- Ad-IL-24 significantly inhibited SGC-7901 cell growth and induced apoptosis, as evidenced by MTT assays and flow cytometry.
- Gene expression analysis revealed that Ad-IL-24 up-regulated pro-apoptotic genes (bax, caspase-3, p53) and down-regulated the anti-apoptotic gene (bcl-2).
Impact:
- Adenovirus-mediated IL-24 expression demonstrates a marked anti-tumor effect on human gastric cancer cells.
- The findings suggest that Ad-IL-24 holds potential as a therapeutic agent for gastric cancer, possibly through modulating the bax/bcl-2 pathway and p53.
- This research provides a foundation for further preclinical and clinical investigations into IL-24-based gene therapy for gastric cancer.
