Kisspeptin Retards Tumor Growth of Lewis Lung Carcinoma Cells Through p38 MAPK-mediated Senescence.

Background/aim: Kisspeptin has multifaceted roles in both normal and pathological conditions. Although lung cancer is a leading cause of cancer worldwide, the role of kisspeptin in lung cancer remains poorly understood. Thus, this study aimed to investigate the effects of kisspeptin on lung cancer.

Materials and methods: Mouse LLC cells were used to examine kisspeptin's effect on cell growth and death. Analyses for apoptosis, cell cycle, and senescence were conducted by flow cytometry, western blots, and immunocytochemistry. An in vivo tumor growth assay was conducted to confirm the effect of kisspeptin on LLC cells.

Results: Kisspeptin reduced LLC cell viability and growth rate. Consistently, kisspeptin arrested LLC cells at G₀/G₁ phase by altering protein levels involved in the cell cycle with no effect on apoptotic cell death. Furthermore, kisspeptin induced senescence of LLC cells. Kisspeptin increased intracellular ROS levels and altered p38 MAPK, AKT, and NF-[Formula: see text]B signaling. Moreover, the p38 MAPK inhibitor SB203580 negated the effects of kisspeptin on cell viability and senescence by blocking kisspeptin-induced phosphorylation of p38 MAPK. In addition, when administered intraperitoneally twice a week to male C57BL/6 mice bearing LLC cells, kisspeptin slowed syngeneic tumor growth without affecting body weight.

Conclusion: Kisspeptin represses mouse lung cancer growth by inducing p38 MAPK-mediated cellular senescence.