title: Leptin regulates proliferation and apoptosis of colorectal carcinoma through PI3K/Akt/mTOR signalling  pathway.
abstract: Epidemiological studies have indicated that obesity is associated with colorectal cancer. The obesity hormone leptin is considered as a key mediator for cancer development and progression. The present study aims to investigate regulatory effects of leptin on colorectal carcinoma. The expression of leptin and its receptor Ob-R was examined by immunohistochemistry in 108 Chinese patients with colorectal carcinoma. The results showed that leptin/Ob-R expression was significantly associated with T stage, TNM stage, lymph node metastasis, distant metastasis, differentiation and expression of p-mTOR, p-70S6 kinase, and p-Akt. Furthermore, the effects of leptin on proliferation and apoptosis of HCT-116 colon carcinoma cells were determined. The results showed that leptin could stimulate the proliferation and inhibit the apoptosis of HCT-116 colon cells through the PI3K/Akt/mTOR pathway. Ly294002 (a PI3K inhibitor) and rapamycin (an mTOR inhibitor) could prevent the regulatory effects of leptin on the proliferation and apoptosis of HCT-116 cells via abrogating leptin-mediated PI3K/Akt/mTOR pathway. All these results indicated that leptin could regulate proliferation and apoptosis of colorectal carcinoma through the PI3K/Akt/ mTOR signalling pathway.
authors.affiliation: Department of Cancer, Xiangya Hospital, Central South University, Changsha 410008, PR China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Zhi
authors.initials: Z
authors.lastname: Duan
authors.forename: Qimei
authors.initials: Q
authors.lastname: Xu
authors.forename: Meiyan
authors.initials: M
authors.lastname: Wei
authors.forename: Lianghua
authors.initials: L
authors.lastname: Wang
authors.forename: Meizuo
authors.initials: M
authors.lastname: Zhong
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D044466:Asian People; D049109:Cell Proliferation; D002867:Chromones / Q000494:pharmacology; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D020738:Leptin / Q000378:metabolism / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D009362:Neoplasm Metastasis / Q000503:physiopathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D002867:Chromones; D020738:Leptin; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D054411:Receptors, Leptin; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546842:MTOR protein, human