肥胖与结直肠癌发病机制的研究进展

doi:10.11904/j.issn.1002-3070.2018.05.016

摘要/Abstract

摘要： 肥胖是由于机体能量长期供过于求,过多的脂肪在体内堆积所致。近年来,随着人们物质水平的提高以及生活习惯的改变,肥胖人群所占的比例越来越多,并成为结直肠癌发生发展的高危因素。肥胖所致结直肠癌发病机制有多种,包括瘦素、脂联素和炎症因子等脂肪因子的作用,以及胰岛素抵抗、miRNA、微量元素、维生素、氧化应激反应和肠道微生态紊乱等方面的原因。本文对其作用机制的研究进展加以综述,以期对结直肠癌的预防和治疗起到积极的指导作用。

关键词: 肥胖, 结直肠癌, 综述

Abstract: Obesity is caused by the long-term supply of energy in the body and the accumulation of excess fat in the body.In recent years,with the improvement of life quality and changes in living habits,the proportion of obese people is increasing,and it is a high risk factor for the development of colorectal cancer.There are many pathogeneses of colorectal cancer caused by obesity,including the action of adipokines such as leptin,adiponectin and inflammatory factor as well as insulin resistance,regulations of miRNA genes,trace elements,vitamin,microelement,oxidative stress response and intestinal microecological disorders.This article reviews the research progress in its mechanism of action,in order to provide guidance for the prevention and treatment of colorectal cancer.

Key words: Obesity, Colorectal cancer, Review

中图分类号:

R735.3+5

刘宏涛, 张彤彤综述, 刘雁军审校. 肥胖与结直肠癌发病机制的研究进展[J]. 实用肿瘤学杂志, 2018, 32(5): 464-467.

LIU Hongtao, ZHANG Tongtong, LIU Yanjun. Research progress in the pathogenesis of obesity and colorectal cancer[J]. PRACTICAL ONCOLOGY JOURNAL, 2018, 32(5): 464-467.

参考文献

1 Kyrgiou M,Kalliala I,Markozannes G,et al.Adiposity and cancer at major anatomical sites:umbrella review of the literature[J].BMJ,2017,356:477.
2 Alexandre L,Long E,Beales IL.Pathophysiological mechanisms linking obesity and esophageal adenocarcinoma[J].World J Gastrointest Pathophysiol,2014,5(4):534-549.
3 Inamura K,Song M,Jung S,et al.Prediagnosis plasma adiponectin in relation to colorectal cancer risk according to KRAS mutation status[J].J Natl Cancer Inst,2016,108(4):363.
4 Moon HS,Liu X,Nagel JM,et al.Salutary effects of adiponectin on colon cancer:in vivo and in vitro studies in mice[J].Gut,2013,62(4):561-570.
5 Nigro E,Schettino P,Polito R,et al.Adiponectin and colon cancer:evidence for inhibitory effects on viability and migration of human colorectal cell lines[J].Mol Cell Biochem,2018[Epub ahead of print].
6 Sahin-Efe A,Upadhyay J,Ko BJ,et al.Irisin and leptin concentrations in relation to obesity,and developing type 2 diabetes:A cross sectional and a prospective case-control study nested in the Normative Aging Study[J].Metabolism,2018,79:24-32.
7 Candelaria PV,Rampoldi A,Harbuzariu A,et al.Leptin signaling and cancer chemoresistance:Perspectives[J].World J Clin Oncol,2017,8(2):106-119.
8 Suman S,Kallakury BV,Fornace AJ,et al.Protracted upregulation of leptin and IGF1 is associated with activation of PI3K/Akt and JAK2 pathway in mouse intestine after ionizing radiation exposure[J].Int J Biol Sci,2015,11(3):274-283.
9 Gremese E,Tolusso B,Gigante MR,et al.Obesity as a risk and severity factor in rheumatic diseases(autoimmune chronic inflammatory diseases)[J].Front Immunol,2014,5:576.
10 Fernandes JV,Cobucci RN,Jatobá CA,et al.The role of the mediators of inflammation in cancer development[J].Pathol Oncol Res,2015,21(3):527-534.
11 Shi G,Zheng X,Zhang S,et al.Kanglaite inhibits EMT caused by TNF-α via NF-κΒ inhibition in colorectal cancer cells[J].Oncotarget,2018,9(6):6771-6779.
12 Zhang X,Hu F,Li G,et al.Human colorectal cancer-derived mesenchymal stem cells promote colorectal cancer progression through IL-6/JAK2/STAT3 signaling[J].Cell Death Dis,2018,9(2):25.
13 Kilic ID,Dodurga Y,Uludag B,et al.MicroRNA-143 and-223 in obesity[J].Gene,2015,560(2):140-142.
14 Jordan SD,Krüger M,Willmes DM,et al.Obesity-induced overexpression of miR-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism[J].Nat Cell Biol,2011,13(4):434-446.
15 Wang G,Gu J,Gao Y.MicroRNA target for MACC1 and CYR61 to inhibit tumor growth in mice with colorectal cancer[J].Tumour Biol,2016,37(10):13983-13993.
16 Ba S,Xuan Y,Long ZW,et al.MicroRNA-27a promotes the proliferation and invasiveness of colon cancer cells by targeting SFRP1 through the Wnt/β-Catenin signaling pathway[J].Cell Physiol Biochem,2017,42(5):1920-1933.
17 Torkanlou K,Bibak B,Abbaspour A,et al.Reduced serum levels of Zinc and superoxide dismutase in obese individuals[J].Ann Nutr Metab,2016,69(3/4):232-236.
18 Habib SA,Saad EA,Elsharkawy AA,et al.Pro-inflammatory adipocytokines,oxidative stress,insulin,Zn and Cu:Interrelations with obesity in Egyptian non-diabetic obese children and adolescents[J].Adv Med Sci,2015,60(2):179-185.
19 Fan Y,Zhang C,Bu J.Relationship between selected serum metallic elements and obesity in children and adolescent in the US[J].Nutrients,2017,9(2):104.
20 Pongkorpsakol P,Moonwiriyakit A,Muanprasat C.Fatty acid and mineral receptors as drug targets for gastrointestinal disorders[J].Future Med Chem,2017,9(3):315-334.
21 Choi S,Cui C,Luo Y,et al.Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through Orai1[J].FASEB J,2018,32(1):404-416.
22 Brady DC,Crowe MS,Turski ML,et al.Copper is required for oncogenic BRAF signalling and tumorigenesis[J].Nature,2014,509(7501):492-496.
23 Walsh JS,Bowles S,Evans AL.Vitamin D in obesity[J].Curr Opin Endocrinol Diabetes Obes,2017,24(6):389-394.
24 Choi MK,Song HJ,Paek YJ,et al.Gender differences in the relationship between vitamin C and abdominal obesity[J].Int J Vitam Nutr Res,2013,83(6):377-384.
25 Barry EL,Peacock JL,Rees JR,et al.Vitamin D receptor genotype,Vitamin D3 supplementation,and risk of colorectal adenomas:A randomized clinical trial[J].JAMA Oncol,2017,3(5):628-635.
26 Zhu Y,Chen P,Gao Y,et al.MEG3 Activated by vitamin D inhibits colorectal cancer cells proliferation and migration via regulating clusterin[J].E Bio Medicine,2018,30:148-157.
27 Yun J,Mullarky E,Lu C,et al.Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH[J].Science,2015,350(6266):1391-1396.
28 Barazzoni R,Gortan CG,Ragni M,et al.Insulin resistance in obesity:an overview of fundamental alterations[J].Eat Weight Disord,2018,23(2):149-157.
29 Tran TT,Naigamwalla D,Oprescu AI,et al.Hyper insulinemia,but not other factors associated with insulin resistance,acutely enhances colorectal epithelial proliferation in vivo[J].Endocrinology,2006,147(4):1830-1837.
30 Chang CK,Ulrich CM.Hyper insulinaemia and hyper glycaemia:possible risk factors of colorectal cancer among diabetic patients[J].Diabetologia,2003,46(5):595-607.
31 Teng JA,Wu SG,Chen JX,et al.The activation of ERK1/2 and JNK MAPK signaling by insulin/IGF-1 is responsible for the development of colon cancer with type 2 diabetes mellitus[J].PLoS One,2016,11(2):e0149822.
32 Paglialunga S,Ludzki A,Root-McCaig J,et al.In adipose tissue,increased mitochondrial emission of reactive oxygen species is important for short-term high-fat diet-induced insulin resistance in mice[J].Diabetologia,2015,58(5):1071-1080.
33 Valko M,Rhodes CJ,Moncol J,et al.Free radicals,metals and antioxidants in oxidative stress-induced cancer[J].Chem Biol Interact,2006,160(1):1-40.
34 Banerjee K,Mandal M.Oxidative stress triggered by naturally occurring flavone apigenin results in senescence and chemotherapeutic effect in human colorectal cancer cells[J].Redox Biol,2015,5:153-162.
35 Kim SH,Kim KH,Yoo BC,et al.Induction of LGR5 by H₂O₂ treatment is associated with cell proliferation via the JNK signaling pathway in colon cancer cells[J].Int J Oncol,2012,41(5):1744-1750.
36 Andoh A,Nishida A,Takahashi K,et al.Comparison of the gut microbial community between obese and lean peoples using 16S gene sequencing in a Japanese population[J].J Clin Biochem Nutr,2016,59(1):65-70.
37 Gao Z,Guo B,Gao R,et al.Probiotics modify human intestinal mucosa-associated microbiota in patients with colorectal cancer[J].Mol Med Rep,2015,12(4):6119-6127.
38 Yu T,Guo F,Yu Y,et al.Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy[J].Cell,2017,170(3):548-563.

[1]	方琳, 刘超, 张纯慧, 张艳桥. 转移性结直肠癌维持治疗的研究现状与治疗策略[J]. 实用肿瘤学杂志, 2019, 33(2): 173-178.
[2]	佟广海, 田洋, 吴华星. 脂质组学在结直肠癌研究中的应用[J]. 实用肿瘤学杂志, 2019, 33(2): 179-192.
[3]	刘恒辰, 张新宇. Toll样受体信号通路作为结直肠癌潜在治疗靶点的研究进展[J]. 实用肿瘤学杂志, 2019, 33(2): 188-192.
[4]	韩帮岭, 汪亦民综述, 薛英威审校. 维生素D在消化系统肿瘤中的研究进展[J]. 实用肿瘤学杂志, 2018, 32(5): 471-475.
[5]	王志, 刘忠卫, 曾雪芸, 隋明洁, 廖静怡, 李月欢, 黄卫东, 刘国祥. 基于EQ-5D-5L的结直肠癌癌前病变患者健康相关生命质量研究[J]. 实用肿瘤学杂志, 2018, 32(4): 320-326.
[6]	崔雪阳, 邢承忠. 液体活检在结直肠癌领域的研究及应用现状[J]. 实用肿瘤学杂志, 2018, 32(4): 367-370.
[7]	李文琪, 耿敬姝. RAS/RAF突变与MSI状态在结直肠癌治疗中的研究进展[J]. 实用肿瘤学杂志, 2018, 32(4): 371-376.
[8]	余嘉惠, 刘煊, 李琦, 陆烨, 岳小强. 长链非编码RNA在胃癌中的调控机制及中药对其作用的研究概况[J]. 实用肿瘤学杂志, 2018, 32(1): 47-52.
[9]	李宏伟, 刘川, 王朗, 刘竣, 杨汉丰, 杜勇. 光动力疗法在消化道恶性肿瘤中的研究进展[J]. 实用肿瘤学杂志, 2018, 32(1): 77-81.
[10]	张姗姗, 吴华星审校. 代谢组学在结直肠癌诊断中的应用[J]. 实用肿瘤学杂志, 2017, 31(6): 573-576.
[11]	孙丽娜, 赵晓迪综述, 卢瑗瑗, 王新审校. LncRNA与胃肠道肿瘤化疗耐药的研究进展[J]. 实用肿瘤学杂志, 2017, 31(5): 448-453.
[12]	王东亮,戚宁,牟冠男,张月桂. 结直肠癌肿瘤微环境中调节性T细胞CD39、CD73亚群及二者双阳性亚群的临床意义[J]. 实用肿瘤学杂志, 2017, 31(4): 329-334.
[13]	郝小军，王传卓，赵相轩，辛鹤，刘兆玉. miR-34a对结肠癌细胞SW480增殖、迁移和侵袭能力的影响及机制探讨[J]. 实用肿瘤学杂志, 2017, 31(3): 193-198.
[14]	靳晶综述，贺宇彤审校. miR-21在食管癌中的研究进展[J]. 实用肿瘤学杂志, 2017, 31(3): 277-280.
[15]	张明, 朱信强, 丁闯, 孔令永, 陈焰. 结直肠癌患者术后预后营养指数在预后评估中的应用[J]. 实用肿瘤学杂志, 2017, 31(2): 131-136.