Targeting Leptin as a Therapeutic Strategy against Ovarian Cancer Peritoneal Metastasis

Title:Targeting Leptin as a Therapeutic Strategy against Ovarian Cancer Peritoneal Metastasis

Volume: 17 Issue: 8

Author(s): Xiao Wei, Yi Liu, Cheng Gong, Teng Ji, Xiaoshui Zhou, Taoran Zhang, Dongyi Wan, Sen Xu, Ping Jin, Xin Yang, Xiaoting Li, Ding Ma, Zongyuan Yang*Qinglei Gao*

Affiliation:

• Cancer Biology Research Center (Key laboratory of the ministry of education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan,China

• Cancer Biology Research Center (Key laboratory of the ministry of education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan,China

Keywords: Leptin, ovarian cancer, metastasis, EMT, PI3K/Akt/mTOR, therapeutic strategy.

Abstract: Background/Aims: Epithelial ovarian cancer (OC) is the leading cause of death in patients with gynecologic malignancy. Malignant ascites, a shared symptom of advanced OC patients, plays an important role in the peritoneal metastasis cascade of OC. Since leptin existed in great amount in malignant ascites, we speculated that it might be involved in the modulation of tumor cells malignant behavior.

Method: Here, we demonstrated that blocking of leptin could significantly suppress ovarian malignant ascitesinduced metastatic aggravation of OC cells. Furthermore, our results suggested that leptin was highly expressed in OC and correlated with poor outcome of OC patients. Recombinant leptin notably promoted the migration, invasion and proliferation of OC cells.

Result: Mechanistically, we found that leptin induced epithelial-mesenchymal transition (EMT) program in OC cells through the activation of the PI3K/Akt/mTOR pathway. Pharmacological inhibition of the PI3K/Akt/mTOR pathway partly impaired leptin-induced malignant transformation of OC cells. More importantly, our in vivo xenograft experiment showed that blocking of leptin could dramatically inhibit OC cells peritoneal dissemination.

Conclusion: Collectively, this study emphasized the importance of leptin in OC progression and illustrated a novel mechanism that the PI3K/Akt/mTOR pathway was involved in leptin-induced EMT. Our findings provide new insights into leptin exertion on OC metastasis and identify the potential of leptin neutralizing as a novel strategy against OC peritoneal dissemination.

Cite this article as:

Wei Xiao, Liu Yi, Gong Cheng, Ji Teng, Zhou Xiaoshui, Zhang Taoran, Wan Dongyi, Xu Sen, Jin Ping, Yang Xin, Li Xiaoting, Ma Ding, Yang Zongyuan*, Gao Qinglei*, Targeting Leptin as a Therapeutic Strategy against Ovarian Cancer Peritoneal Metastasis, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (8) . https://dx.doi.org/10.2174/1871520616666161221114454

DOI https://dx.doi.org/10.2174/1871520616666161221114454	Print ISSN 1871-5206
Publisher Name Bentham Science Publisher	Online ISSN 1875-5992