Protective Effects of Relaxin 2 (RLXH2) against Hypoxia-Induced Oxidative Damage and Cell Death via Activation of The Nrf2/HO-1 Signalling Pathway in Gastric Cancer Cells.

Abstract

This study aims to investigate the potential role of relaxin, a peptide hormone, in preventing cellular deterioration and death in gastric carcinoma cells under hypoxic conditions. It explores the effects of recombinant relaxin 2 (RLXH2) on growth, cell differentiation, invasive potential, and oxidative damage in these cells. In this experimental study, the NCI-N87 cell line was cultured under normal conditions and then subjected to hypoxia using cobalt chloride (CoCl2). The cells were treated with RLXH2, and various assays were performed to assess cellular deterioration, death, and oxidative stress. Western blot and quantitative real time polymerase chain reaction (qRT-PCR) were used to measure the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1, and the translocation of Nrf2 to the nucleus was confirmed through Western blot analysis. This study demonstrates, for the first time, that RLXH2 significantly reduces the formation of reactive oxygen species (ROS) and the release of lactate dehydrogenase (LDH) in gastric cancer cells under hypoxic conditions. RLXH2 also enhances the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), leading to a decrease in hypoxia-induced oxidative damage. RLXH2 promotes the translocation of Nrf2 to the nucleus, resulting in HO-1 expression. Our findings suggest that RLXH2 plays a significant protective role against hypoxia-induced oxidative damage in gastric carcinoma cells through the Nrf2/HO-1 signalling pathway. This research contributes to a better understanding of the potential therapeutic applications of RLXH2 in gastric cancer treatment.