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.
