NFATc3 mediates the sensitivity of gastric cancer cells to arsenic sulfide

// Xiuli Zhang 1 , Ting Kang 1 , Lian Zhang 1 , Yingying Tong 1 , Wenping Ding 1 and Siyu Chen 1 1 Department of Oncology, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China Correspondence to: Siyu Chen, email: siyu.chen@shsmu.edu.cn Keywords: As 4 S 4 , NFATc3, c-Myc, sensitivity, gastric cancer Abbreviations: As 4 S 4 : arsenic sulfide; NFAT: nuclear factor of activated T cells; GC: gastric cancer; PML: promyelocytic leukemia Received: December 07, 2016      Accepted: March 03, 2017      Published: April 18, 2017 ABSTRACT Arsenic sulfide (As 4 S 4 ) is the main component of Realgar which is widely used in traditional Chinese medicine. Previously we showed that As 4 S 4 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 As 4 S 4 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 As 4 S 4 was dissimilar, with AGS and MGC803 cells showing higher sensitivity while the SGC7901 cells relatively resistant. Interestingly, the sensitivity to As 4 S 4 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, As 4 S 4 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.