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内容記述 |
KRAS mutations occur primarily in the non-small cell lung cancer (NSCLC), and the presence of KRAS mutations is associated with poor prognosis. In this study we investigate the effects of a multi-ion (He-, C-, O-, Ne-) beam irradiation (IR) alone or in combination with KRASG12C inhibitors (sotorasib, adagrasib) on NSCLC cells. We found that LU99 (KRASG12C mutant) and A549 (KRASG12S mutant) cells were resistant to He and C-ion beam IR, but sensitive to Ne-ion beam IR, which was ineffective when combined with sotrasib or adagrasib. In contrast, LU65 (KRASG12C mutant) cells were sensitive to treatment with C-, Ne- and O-ion beam IR alone, and was further enhanced when combined with sotorasib or adagrasib, whereas LU99 cells were killed by C-, Ne-ion beam combined with relatively high dose of sotorasib or adagrasib. Furthermore, C-, and Ne-ion beam IR in combination with sotorasib significantly enhanced the expression of the apoptosis- and autophagy-related genes such as cleaved-caspase3 and ATG7. Taken together, combination of heavier ions such as Ne-ion IR, with KRAS12C inhibitors likely induces KRASG12C mutant NSCLC cell death more significantly. |
