IL-24 inhibits endometrial cancer cell proliferation by promoting apoptosis through the mitochondrial intrinsic signaling pathway

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.

Keywords: Antitumor; Cell apoptosis; Endometrial cancer; IL-24; Mitochondrial intrinsic signaling pathway.