Leptin promotes proliferation and metastasis of human gallbladder cancer through OB-Rb leptin receptor

Zou,Hao; Liu,Yunxia; Wei,Dong; Wang,Tao; Wang,Kun; Huang,Songquan; Liu,Lixin; Li,Yuehua; Ge,Jiayun; Li,Xiao; Zhu,Hong; Wang,Lianmin; Zhao,Songling; Zhang,Xiaowen; Wang,Lin

doi:10.3892/ijo.2016.3530

Leptin promotes proliferation and metastasis of human gallbladder cancer through OB-Rb leptin receptor

Authors:
- Hao Zou
- Yunxia Liu
- Dong Wei
- Tao Wang
- Kun Wang
- Songquan Huang
- Lixin Liu
- Yuehua Li
- Jiayun Ge
- Xiao Li
- Hong Zhu
- Lianmin Wang
- Songling Zhao
- Xiaowen Zhang
- Lin Wang
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Affiliations: Department of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650101, P.R. China, Experiment Teaching Center, Basic Medical School, Kunming Medical University, Kunming, Yunnan 650500, P.R. China
Published online on: May 18, 2016 https://doi.org/10.3892/ijo.2016.3530
Pages: 197-206

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Abstract

Emerging evidence has shown that leptin, an adipocyte-derived cytokine that is closely associated with obesity, play a significant role in carcinogenesis and tumorigenesis. However, its impact on gallbladder cancer (GBC) remains unclear. In this study, we firstly found that leptin and its functional receptor OB-Rb were significantly co-expressed in human GBC tissues and cell lines, the content of which were higher than those in normal human gallbladder tissues. Treatment with leptin promoted the proliferation, migration and invasion of GBC cells, which were attenuated by OB-Rb shRNA. Blocking in the G2/M period of cell cycle, increasing of MMP3 and MMP9, increasing of VEGF-C/D, activation of SOCS3/JAK2/p-STAT3 pathway was demonstrated after treatment with leptin. All of these positive responses were attenuated by OB-Rb receptor shRNA. Taken together, our findings suggest that leptin promoted the proliferation, migration and invasion of GBC cells by increasing OB-Rb expression through the SOCS3/JAK2/p-STAT3 signal pathway. Targeting the leptin/OB-Rb axis could be an attractive therapeutic strategy for treatment of GBC.

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