Anticancer effect of exogenous hydrogen sulfide in cisplatin‑resistant A549/DDP cells.

Despite huge advances in lung cancer treatment, resistance to cisplatin‑based chemotherapy remains one of the major obstacles, and the elucidation of cisplatin resistance remains challenging. As an important biological and pharmacological mediator, hydrogen sulfide (H2S) performs a variety of homeostatic functions related to cancer formation and development. However, the effects of H2S on cisplatin‑resistance lung cancer remain largely unknown. In the present study, we investigated the anticancer effects and relevant mechanisms of NaHS (an exogenous donor of H2S) on A549/DDP cells (cisplatin‑resistant). The intracellular H2S was first evaluated using a fluorescence probe in A549 (cisplatin‑sensitive) and A549/DDP cells. We found that H2S production was markedly decreased in A549/DDP cells compared with that in A549 cells, accomplished by the downregulation of cystathionine β‑synthase (CBS), an endogenous H2S‑producing enzyme. In view of these findings, we then observed the effects of NaHS treatment on A549/DDP cells. The results showed that NaHS exposure exhibited an inhibitory effect on cell viability and the IC50 of cisplatin in A549/DDP cells decreased markedly during NaHS treatment (800 µmol/l). In addition, our data revealed that NaHS treatment of A549/DDP cells resulted in the induction of apoptosis, cell cycle arrest and inhibition of cell migration and invasion. Finally, we demonstrated that the marked changes in the A549/DDP cell response to NaHS may be triggered by the activation of p53, and overexpression of p21, caspase‑3, Bax and MMP‑2, as well as the downregulation of Bcl‑xL. The findings of the present study provide novel evidence that NaHS administration may represent a new strategy for the treatment of cisplatin‑resistant lung cancer.