Dose-Dependent Inhibitory Effects of Interleukin-۲۴ (IL-۲۴/MDA-۷) on the PI۳K/AKT/mTOR Signaling Pathway in A۴۳۱ Skin Carcinoma Cells: Implications for Targeted Cancer Therapy

Interleukin-۲۴ (IL-۲۴), also known as melanoma differentiation-associated gene-۷ (MDA-۷), is a multifunctional cytokine with well-documented antitumor properties. This study investigated the dose-dependent effects of IL-۲۴ on the expression of key genes involved in the PI۳K/AKT/mTOR signaling pathway in A۴۳۱ human skin carcinoma cells. A۴۳۱ cells were divided into three control groups and three treatment groups and exposed to IL-۲۴ at concentrations of ۵۰, ۱۰۰, and ۲۰۰ ng/mL for ۲۴ h. Morphological changes were evaluated by light microscopy, while the relative mRNA expression levels of PI۳K, AKT۱, and mTOR were quantified using real-time quantitative polymerase chain reaction (qRT-PCR) following normalization to a housekeeping gene. Treatment with ۲۰۰ ng/mL IL-۲۴ significantly downregulated the expression of all three target genes compared with the untreated controls. The expression levels of PI۳K, AKT۱, and mTOR decreased to ۰.۳۰-fold (P = ۰.۰۰۰۲), ۰.۵۲-fold (P = ۰.۰۰۸۸), and ۰.۳۶-fold (P = ۰.۰۲۲), respectively. At ۱۰۰ ng/mL, IL-۲۴ significantly reduced AKT۱ expression (۰.۶۵-fold, P = ۰.۰۳۶), whereas the changes in PI۳K and mTOR expression were not statistically significant. These findings demonstrate a dose-dependent inhibitory effect of IL-۲۴ on the PI۳K/AKT/mTOR signaling pathway. Overall, IL-۲۴ markedly suppressed the expression of genes associated with cell proliferation and survival, providing further molecular evidence for its antitumor activity in skin carcinoma cells. These results suggest that IL-۲۴ may serve as a promising targeted therapeutic candidate for skin cancer, although additional studies investigating protein expression and in vivo efficacy are required to further validate its therapeutic potential

کلیدواژه ها:

Interleukin-۲۴ ، MDA-۷ ، PI۳K/AKT/mTOR pathway ، A۴۳۱ cells ، skin carcinoma ، antitumor activity