TS-1 inhibits endometrial cancer cell proliferation, migration, and apoptosis by blocking the PI3K/AKT/mTOR signaling pathway.

BACKGROUND: TS-1, an oral fluoropyrimidine-based antitumor agent, is widely used as a first-line therapy for various cancers. This study aimed to investigate the effects and underlying molecular mechanisms of TS-1 on endometrial cancer (EC) cell progression. METHODS: HEC-1-A and Ishikawa EC cell lines were treated with different doses of TS-1 (0, 5, 10, 25, and 50 μg/mL). Cell viability, proliferation, migration, invasion, and apoptosis were assessed. The expression levels of Bcl-2-associated X protein (Bax; pro-apoptotic protein), B-cell lymphoma 2 (Bcl-2; anti-apoptotic protein), and key proteins in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) signaling pathway were analyzed. Furthermore, rescue experiments were performed using the PI3K activator 740 Y-P to determine whether TS-1 inhibits EC cell progression via the PI3K/AKT/mTOR pathway. RESULTS: TS-1 treatment markedly inhibited EC cell proliferation, migration, and invasion, while increasing apoptosis. The half-maximal inhibitory concentration (IC(50)) values of TS-1 for Ishikawa and HEC-1-A cells were 16.26 μg/mL and 11.33 μg/mL, respectively. Moreover, TS-1 induced Bax but suppressed Bcl-2 expression. In addition, TS-1 inhibited the phosphorylation of AKT, PI3K, and mTOR. Treatment with the PI3K activator 740 Y-P reversed the inhibitory effects of TS-1 on EC cell malignant behaviors. CONCLUSION: TS-1 suppresses proliferation, migration, and invasion while promoting apoptosis in EC cells by suppressing the PI3K/AKT/mTOR signaling pathway. These data indicate that TS-1 may serve as a promising therapeutic agent for EC.