作者：Malvi P, Chaube B, Pandey V, Vijayakumar MV, Boreddy PR, Mohammad N, Singh SV, Bhat MK
【摘自】分子腫瘤雜志，2015年第9卷3期。
【文獻摘要】
該項研究通過建立動物模型發(fā)現(xiàn)：無論是奧利司他治療還是控制卡路里攝入量都能明顯延緩黑色素瘤的發(fā)展。在肥胖老鼠身上，降低腫瘤的進展與脂肪的減少有關。因為肥胖導致的腫瘤惡化被降低了，這在實驗組及其對應的對照組中得到了驗證。
在腫瘤中，脂肪酸合酶（FASN）蛋白水平、窖蛋白(Cav)-1和pAkt，這些都是肥胖狀態(tài)下黑色素瘤快速發(fā)展的促進分子，脂肪細胞因子（瘦素和抵抗素）通過激活蛋白激酶（Akt）和調(diào)節(jié)脂肪酸合酶（FASN）、窖蛋白(Cav)-1來促進黑色素瘤細胞生長和增值。在實驗中，這些腫瘤促進分子都被降低了。另外，在使用奧利司他治療和/或控制卡路里攝入的肥胖老鼠的腫瘤細胞中，觀察到了增加壞死和降低血管生成以及增值標記物增殖細胞核抗原（PCNA）和細胞周期蛋白（cyclin D1）。
研究還發(fā)現(xiàn)，來自奧利司他治療的脂肪細胞中的黑色素瘤細胞在培養(yǎng)基（CM）中的生長速度降低了。研究發(fā)現(xiàn)控制體重降低脂肪含量能降低黑色素瘤的發(fā)展。因此，通過降低卡路里攝入或奧利司他治療控制體重能夠降低肥胖導致的腫瘤惡化，延長患者的生存時間。
【文獻原文】
Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: role ofadipokines
Author: Malvi P1, Chaube B1, Pandey V1, Vijayakumar MV1, Boreddy PR1, Mohammad N1, Singh SV1, Bhat MK2.
Author information：
1National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India.
2National Centre for Cell Science, Savitribai Phule Pune University Campus, Ganeshkhind, Pune 411 007, India.
Quote From: Mol Oncol. 2015 Mar;9(3):689-703.
【ABSTRACT】
Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well as progression. Although a few studies have attempted to understand the relationship between obesity and melanoma, the consequences of controlling body weight by reducing adiposity on cancer progression is not well understood. By employing animal models of obesity, we report that controlling obesity either by orlistat treatment or by restricting caloric intake significantly slows down melanoma progression. The diminished tumor progression was correlated with decreased fat mass (adiposity) in obese mice. Obesity associated factors contributing to tumor progression were decreased in the experimental groups compared to respective controls. In tumors, protein levels of fatty acid synthase (FASN), caveolin (Cav)-1 and pAkt, which are tumor promoting molecules implicated in melanoma growth under obese state, were decreased. In addition, increased necrosis and reduction in angiogenesis as well as proliferative markers PCNA and cyclin D1 were observed in tumors of the orlistat treated and/or calorically restricted obese mice. We observed that growth of melanoma cells cultured in conditioned medium (CM) from orlistat-treated adipocytes was reduced. Adipokines (leptin and resistin), via activating Akt and modulation of FASN as well as Cav-1 respectively, enhanced melanoma cell growth and proliferation. Together, we demonstrate that controlling body weight reduces adipose mass thereby diminishing melanoma progression. Therefore, strategic means of controlling obesity by reduced caloric diet or with antiobesity drugs treatment may render obesity-promoted tumor progression in check and prolong survival of patients.