NFATc3 mediates the sensitivity of gastric cancer cells to arsenic sulfide.

Arsenic sulfide (As4S4) is the main component of Realgar which is widely used in traditional Chinese medicine. Previously we showed that As4S4 inhibited the proliferation of colon cancer cells through regulating nuclear factor of activated T cells (NFAT) pathway. Here we explore the role of NFAT in gastric cancer. We showed that As4S4 inhibited the expression of NFATc1, NFATc3, and NFATc4, and modulated the expression of NFATc2 accompanying with p53. The baseline expression of NFATc3 varied distinctly in gastric cancer cell lines (AGS, MGC803, MKN28, MKN45, and SGC7901) and the sensitivity of these cells to As4S4 was dissimilar, with AGS and MGC803 cells showing higher sensitivity while the SGC7901 cells relatively resistant. Interestingly, the sensitivity to As4S4 was correlated with the level of expression of NFATc3, and the cells relatively sensitivity just showing higher expression of NFATc3. Furthermore, NFATc3 expression was significantly higher in gastric cancer tissues compared with the adjacent normal tissues. Our data also showed that, NFATc3 promoted the proliferation of gastric cancer cells by regulating c-Myc. In conclusion, As4S4 inhibited the proliferation of gastric cancer cells through NFATc3/c-Myc pathway and the diverse sensitivity among different cell lines correlated with the expression level of NFATc3 indicating that NFATc3 may be a potential therapeutic target in gastric cancer.