Aspirin overcomes cisplatin resistance in lung cancer by inhibiting cancer cell stemness

BACKGROUND: Lung cancer is the leading cause of cancer death and is commonly treated by cisplatin. Although cisplatin treatment may initially be successful, its effectiveness usually reduces significantly in disease‐recurrent patients. Aspirin, a nonselective COX inhibitor, has been shown to help reverse the status of cisplatin sensitivity in recurrent human ovarian cancer cells. This study aimed to explore the effect of aspirin on cisplatin resistance through the perspective of cancer cell stemness. METHODS: We used clustering analysis to predict the H460 cisplatin resistance from the GSE21656 dataset. The increased lung cancer cell stemness may contribute to enhanced tolerance. In this study, we used aspirin, a nonselective COX inhibitor, with cisplatin for several hours in cells and days in vivo, and studied the inhibition against human cisplatin‐resistant H460 cells. H460 cisplatin‐sensitive and H460 cisplatin‐resistant cells were treated with 16 μM aspirin or/and 0.3 μg/mL cisplatin for 72 hours. RESULTS: H460 cisplatin‐resistant cells showed stronger resistance, stemness, and invasiveness than H460 cisplatin‐sensitive, and cisplatin significantly reduced the survival of cisplatin‐sensitive cells, while cisplatin with aspirin dramatically reduced the surviving fractions of cisplatin‐resistant cells. CONCLUSIONS: This study revealed that stemness is a latent inhibitor of the resistance of lung cancer cisplatin‐resistant cells and might be effectively inhibited by aspirin.