SHP099 Combination Inhibits the Malignant Biological Behavior of L-OHP/5-fu Resistant Colorectal Cancer Cells by Regulating Energy Metabolism Reprogramming

Abstract Methods HT29 and SW480 cell lines were fostered in media containing L-OHP or 5-Fu to establish drug-resistant strains. Injected subcutaneously HT29 and SW480 drug-resistant cells into the ventral of nude mice at a dose of 5 × 10 6 to establish CRC drug-resistant animal models. CCK-8, Western blot, flow cytometry, Transwell and kit detection were used to detect the regulation mechanism of energy metabolism reprogramming in drug-resistant CRC cells. Results: Compared with non-resistant strains, L-OHP/5-fu resistant strains had stronger ability of metabolic reprogramming. Functionally, SHP099 can restrain the metabolic reprogramming of L-OHP/5-fu resistant strains, and then restrain the cell proliferation, cloning, migration and tumor spheroid formation of L-OHP/5-fu resistant strains. Downstream mechanism studies have shown that SHP099 interferes with the metabolic reprogramming of L-OHP/5-fu drug-resistant strains by suppressing PI3K/AKT pathway, thereby restraining the malignant biological behavior of L-OHP/5-fu drug-resistant strains and alleviating CRC. Conclusion: The combination of SHP099 can restrain the malignant biological behavior of L-OHP/5-fu resistant CRC cells and alleviate the progression of CRC by interfering with the reprogramming of energy metabolism.