JH-RE-06 enhances the inhibitory effect of cisplatin on cancer cell survival and anti-tumour activity: metabolic regulation impact

BACKGROUND: Gastric cancer is a highly prevalent malignant tumour worldwide. Platinum-based chemotherapy, with cisplatin as the core, is the main treatment option for advanced gastric cancer. However, inherent or acquired drug resistance severely restricts clinical efficacy. PURPOSE AND METHOD: The study used REV1-highly-expressed human gastric cancer AGS and HGC-27 cells and subcutaneous xenograft tumours in nude mice as models, combined with cell function experiments, molecular biology detection and non-targeted metabolomics technology, to analyse the anti-tumour effect of JH-RE-06 combined with cisplatin, systematically explore the regulatory characteristics of the combined treatment on metabolic networks such as glycolysis. RESULTS: The results showed that JH-RE-06 could significantly enhance the proliferation inhibition, G2/M cell cycle arrest, apoptosis induction and DNA damage effects of gastric cancer cells by cisplatin. CONCLUSION: SDF4 overexpression could reverse the above metabolic abnormalities by activating the Akt/mTOR pathway, partially restoring cell metabolic homeostasis and DNA damage tolerance, and weakening the anti-tumour effect of combined treatment.