IL-24 inhibits endometrial cancer cell proliferation by promoting apoptosis through the mitochondrial intrinsic signaling pathway - 11/02/20
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Graphical abstract |
Highlights |
• | High expression levels of IL-24 in human endometrial cancer tissues. |
• | IL-24 induced endometrial cancer cells apoptosis. |
• | IL-24 inhibited endometrial cancer cell invasion and tumor angiogenesis. |
• | IL-24 inhibited endometrial cancer by mitochondrial intrinsic signaling pathway. |
• | The first proof of principle for mechanism of IL24 on endometrial cancer. |
Abstract |
Background |
Endometrial cancer is a type of malignant tumor of the female reproductive system. Preserving fertility in endometrial cancer patients is currently a formidable challenge. Interleukin-24 (IL-24) is a unique cytokine tumor suppressor gene belonging to the IL-10 cytokine family. IL-24 has broad-spectrum antitumor activity through different signaling pathways but does not affect normal cells. IL-24 gene therapy may provide a new method for the treatment of endometrial cancer.
Methods |
Transfection was used for gene transfer. The expression of IL-24 and related pathway proteins in endometrial cancer tissue and the Ishikawa cell line was detected by immunohistochemistry and Western blotting, respectively. The antitumor function of IL-24 was examined in vitro and in vivo. Cell proliferation was determined by CCK-8 assay, cell migration was shown by wound-healing assay, and cell invasion was detected by Transwell assay. Apoptosis was analyzed by TUNEL assay, and HE staining was performed to observe the morphology of the samples.
Results |
Immunohistochemical analysis showed different expression levels of IL-24 in human endometrial cancer tissues and normal endometrial tissues. IL-24 increased protein expression of BAX and Cytochrome C, while BCL-2, MMP-3, VEGF, Caspase-9 and Caspase-3 expression was decreased. Overexpression of IL-24 inhibited cell proliferation, migration and invasion, but increased cell apoptosis in endometrial cancer. Mechanistically, we demonstrated that IL-24 inhibited endometrial cancer cell growth by inducing cell apoptosis through the mitochondrial intrinsic signaling pathway. In addition, IL-24 inhibited tumor development by inducing cell apoptosis and inhibiting angiogenesis, as shown in xenograft tumor experiments.
Conclusions |
Our study demonstrates the antitumor effect of IL-24 on endometrial cancer and shows that IL-24 may be a promising therapeutic gene for endometrial cancer gene therapy.
Le texte complet de cet article est disponible en PDF.Abbreviations : IL-24, MDA-7, GAPDH, HE, IHC, TUNEL, VEGF, MOMP, Apaf-1
Keywords : IL-24, Endometrial cancer, Cell apoptosis, Mitochondrial intrinsic signaling pathway, Antitumor
Plan
Vol 124
Article 109831- avril 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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