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TS-1 inhibits endometrial cancer cell proliferation, migration, and apoptosis by blocking the PI3K/AKT/mTOR signaling
Ya'nan Si1, Deyan Wang2, Zhongxiu Li1
1Department of Gynecology I, Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University Qingdao 266033, Shandong, China.
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 (IC50) 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.
Insights
TS-1 effectively inhibits endometrial cancer (EC) cell progression by suppressing the PI3K/AKT/mTOR pathway, leading to reduced proliferation and migration while increasing apoptosis. This suggests TS-1 as a potential therapeutic agent for EC.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- TS-1 is an oral fluoropyrimidine-based antitumor agent used for various cancers.
- Endometrial cancer (EC) progression requires investigation into novel therapeutic strategies.
- Understanding TS-1's molecular mechanisms in EC is crucial for its potential application.
Purpose of the Study:
- To investigate the effects of TS-1 on endometrial cancer (EC) cell progression.
- To elucidate the underlying molecular mechanisms of TS-1 action in EC cells.
- To evaluate TS-1 as a potential therapeutic agent for EC.
Main Methods:
- EC cell lines (HEC-1-A and Ishikawa) were treated with varying doses of TS-1.
- Assessed cell viability, proliferation, migration, invasion, and apoptosis.
- Analyzed expression of apoptosis-related proteins (Bax, Bcl-2) and PI3K/AKT/mTOR pathway components.
- Conducted rescue experiments using a PI3K activator (740 Y-P).
Main Results:
- TS-1 significantly inhibited EC cell proliferation, migration, and invasion, while promoting apoptosis.
- TS-1 altered the expression of Bax and Bcl-2, indicating an apoptotic effect.
- TS-1 suppressed the phosphorylation of key proteins in the PI3K/AKT/mTOR pathway.
- PI3K activation reversed the inhibitory effects of TS-1, confirming pathway involvement.
Conclusions:
- TS-1 suppresses EC cell proliferation, migration, and invasion by inhibiting the PI3K/AKT/mTOR signaling pathway.
- TS-1 promotes apoptosis in EC cells through modulation of this pathway.
- TS-1 demonstrates potential as a promising therapeutic agent for endometrial cancer.
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