OBJECTIVE  To investigate the antitumor activities and mechanisms of the combination of KRAS G12C inhibitors and AKT inhibitor capivasertib against KRAS G12-mutant tumor cells.

METHODS Taking KRAS G12C mutation cell lines, including human pancreatic cancer cell line MIA-PACA2 and human non-small cell lung cancer NCI-H358 as in vitro model, the CCK8 assay, flow cytometry, Western blotting, colony formation assay were performed to investigate the effects of KRAS G12C inhibitor in combination with capivasertib or alone on cell proliferation inhibition, cell cycle apoptosis, the expression of intracellular related proteins and the ability of colony formation, respectively.

RESULTS The combination of KRAS G12C inhibitor and capivasertib significantly enhanced the inhibition of tumor cell proliferation, cell migration, and colony formation, and down-regulated the activation or expression of AKT pathway and ERK pathway-related proteins in a concentration-dependent manner, thereby inducing cell cycle arrest and apoptosis of tumor cells.

CONCLUSION The combination of KRAS G12C inhibitor and capivasertib has synergistic effects on KRAS G12C mutant tumor cells, and exerts significant antitumor activities through inducing cell cycle arrest and apoptosis.