- 作者: Yu-Tang Chin, Le-Ming Wang, Meng-Ti Hsieh, Ya-Jung Shih, André Wendindondé Nana, Chun A. Changou, Yu-Chen S. H. Yang, Hsien-Chung Chiu, Earl Fu, Paul J. Davis, Heng-Yuan Tang and Hung-Yun Lin
- 作者服務機構: 1. Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan 2. PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, 250 Wu-Hsing Street, Taipei 11031, Taiwan
- 中文摘要:
- 英文摘要:
Background
Obesity and its comorbidities constitute a serious health burden worldwide. Leptin plays an important role in diet control; however, it has a stimulatory potential on cancer cell proliferation. The OB3 peptide, a synthetic peptide, was shown to be more active than leptin in regulating metabolism but with no mitogenic effects in cancer cells.
Methods
In this study, we investigated the proliferative effects, gene expressions and signaling pathways modulated by leptin and OB3 in human ovarian cancer cells. In addition, an animal study was performed.
Results
Leptin, but not OB3, induced the proliferation of ovarian cancer cells. Interestingly, OB3 blocked the leptin-induced proliferative effect when it was co-applied with leptin. Both leptin and OB3 activated the phosphatidylinositol-3-kinase (PI3K) signal transduction pathway. In addition, leptin stimulated the phosphorylation of signal transducer and activator of transcription-3 (STAT3) Tyr-705 as well as estrogen receptor (ER)α, and the expression of ERα-responsive genes. Interestingly, all leptin-induced signal activation and gene expressions were blocked by the co-incubation with OB3 and the inhibition of extracellular signal-regulated kinase (ERK)1/2. Coincidently, leptin, but not OB3, increased circulating levels of follicle-stimulating hormone (FSH) which is known to play important roles in the initiation and proliferation of ovarian cancer cells.
Conclusions
In summary, our findings suggest that the OB3 peptide may prevent leptin-induced ovarian cancer initiation and progression by disrupting leptin-induced proliferative signals via STAT3 phosphorylation and ERα activation. Therefore, the OB3 peptide is a potential anticancer agent that might be employed to prevent leptin-induced cancers in obese people. - 中文關鍵字:
- 英文關鍵字: Obesity, Leptin, OB3-leptin peptide, Ovarian cancer