Suppression of autophagy facilitates hydrogen gas-mediated lung cancer cell apoptosis

Our previous study found that hydrogen gas (H(2)) could efficiently inhibit lung cancer progression; however, the underlying mechanisms still remains to be elucidated. The present study aimed to explore the roles of H(2) in lung cancer cell autophagy, and reveal the effects of autophagy on H(2)-mediated lung cancer cell apoptosis and the underlying mechanisms. The expression levels of proteins associated with cell apoptosis and autophagy were detected using western blot analysis. Cell autophagy was inhibited by 3-methyladenine treatment or Beclin1 downregulation, while rapamycin was used to induce autophagy. Cell growth and apoptosis were detected using the Cell Counting Kit-8 and flow cytometry assays, respectively. The results demonstrated that cell apoptosis and autophagy were significantly enhanced in the A549 and H1975 lung cancer cell lines treated with H(2). However, autophagy enhancement weakened H(2) roles in promoting cell apoptosis and vice versa. In addition, it was found that H(2) treatment induced marked decreases in the protein expression levels of phosphorylated STAT3 and Bcl2, and overexpression of STAT3 abolished H(2) roles in promoting cell apoptosis and autophagy. Overall, the present study revealed that H(2) can promote lung cancer cell apoptosis and autophagy via inhibiting the activation of STAT3/Bcl2 signaling and suppression of autophagy can enhance H(2) roles in promoting lung cancer cell apoptosis.