Malih Sara, Najafi Rezvan
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Tumour Biol. 2015 Sep;36(9):6673-5. doi: 10.1007/s13277-015-3911-3. Epub 2015 Aug 18.
Colorectal cancer (CRC) is in the third place of the most common cancers. Certain risk factors can increase the development of CRC, including diet and inheritance. Several studies have shown that there is a potential link between obesity and CRC. Adipose tissue is known to be a largest endocrine organ in the body, with the ability to produce various cytokines including adiponectin. Two types of adiponectin receptor, AdipoR1 and AdipoR2, have been detected in various cancer tissues such as CRC. There is mounting evidence that AdipoR1 signaling occurs mainly through 5' AMP-activated protein kinase (AMPK) and adiponectin inhibits colorectal cancer cell growth via activation of AMPK, thereby suppression of the mammalian target of rapamycin (mTOR) pathway. Thus, adiponectin replacement-based therapies may represent a novel approach in CRC cell growth inhibition in early stages. AdipoRon is an adiponectin-like synthetic small molecule that activated both adiponectin receptors 1 and 2. We hypothesize that AdipoRon has antiproliferative effects of adiponectin and may suppress the CRC cell growth. With clarification of this drug's role in CRC, it can be used as chemoprevention in patients at risk of developing the disease.
结直肠癌(CRC)是最常见的癌症中位列第三的癌症。某些风险因素会增加结直肠癌的发病几率,包括饮食和遗传因素。多项研究表明,肥胖与结直肠癌之间存在潜在联系。脂肪组织是人体最大的内分泌器官,能够产生包括脂联素在内的多种细胞因子。在包括结直肠癌在内的多种癌症组织中已检测到两种脂联素受体,即脂联素受体1(AdipoR1)和脂联素受体2(AdipoR2)。越来越多的证据表明,AdipoR1信号传导主要通过5' 腺苷酸活化蛋白激酶(AMPK)进行,脂联素通过激活AMPK来抑制结肠癌细胞生长,从而抑制雷帕霉素靶蛋白(mTOR)通路。因此,基于脂联素替代的疗法可能是早期抑制结直肠癌细胞生长的一种新方法。AdipoRon是一种类似脂联素的合成小分子,可激活脂联素受体1和2。我们假设AdipoRon具有脂联素的抗增殖作用,可能会抑制结直肠癌细胞生长。随着这种药物在结直肠癌中作用的明确,它可用于对有患该病风险的患者进行化学预防。