奥利司他治疗和饮食干预能减少脂肪量,从而逆转肥胖导致的黑色素瘤恶化

2016-07-20 14:36:08

所属分类:专业学术



作者:Malvi P, Chaube B, Pandey V, Vijayakumar MV, Boreddy PR, Mohammad N, Singh SV, Bhat MK

【摘自】分子肿瘤杂志,2015年第9卷3

【文献摘要】

该项研究通过建立动物模型发现:无论是奥利司他治疗还是控制卡路里摄入量都能明显延缓黑色素瘤的发展。在肥胖老鼠身上,降低肿瘤的进展与脂肪的减少有关。因为肥胖导致的肿瘤恶化被降低了,这在实验组及其对应的对照组中得到了验证。
在肿瘤中,脂肪酸合酶(FASN)蛋白水平、窖蛋白(Cav)-1和pAkt,这些都是肥胖状态下黑色素瘤快速发展的促进分子,脂肪细胞因子(瘦素和抵抗素)通过激活蛋白激酶(Akt)和调节脂肪酸合酶(FASN)、窖蛋白(Cav)-1来促进黑色素瘤细胞生长和增值。在实验中,这些肿瘤促进分子都被降低了。另外,在使用奥利司他治疗和/或控制卡路里摄入的肥胖老鼠的肿瘤细胞中,观察到了增加坏死和降低血管生成以及增值标记物增殖细胞核抗原(PCNA)和细胞周期蛋白(cyclin D1)。
研究还发现,来自奥利司他治疗的脂肪细胞中的黑色素瘤细胞在培养基(CM)中的生长速度降低了。研究发现控制体重降低脂肪含量能降低黑色素瘤的发展。因此,通过降低卡路里摄入或奥利司他治疗控制体重能够降低肥胖导致的肿瘤恶化,延长患者的生存时间。

【文献原文】

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.

 

文献详情:http://www.ncbi.nlm.nih.gov/pubmed/?term=Obesity+induced+rapid+melanoma+progression+is+reversed+by+orlistat+treatment+and+dietary+intervention%3A+role+ofadipokines