Effect and Mechanism of Apple Polysaccharides on Experimental Colitis Associated Colorectal Cancer in Mice
ZHANG Dian1a,2,WANG Fen-xia3, MI Man1b, SUN Yang 2 ,LI Yu-hua2, FAN Lei2, LIU Li1, MEI Qi-bing2*
1.a.Department of Pathogen Biology and Immunology; b.Department of Pharmacology,Xi��an Medical University, Xi��an 710021,China; 2. Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi��an 710032, China; 3. Department of Pharmacy, Shaanxi Friendship Hospital,Xi��an 710068,China
Abstract��OBJECTIVE To study the effects and mechanisms of apple polysaccharides(AP) on tumorigenesis in a mouse model of colitis-associated colon cancer. METHODS AP was obtained from apple pomace and its protective efficacy was evaluated on carcinogenesis in a mouse model of colitis-associated colon cancer induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). The effects of AP on TLR4/MyD88/NF-��B pathway were measured using immunohistochemistry , ELISA and Western blot.The serum were collected and TNF-�� was measured by ELISA kits. RESULTS After 20 weeks of continuous treatment, the incidence of colon cancer formation was 95% in the mice treated with AOM/DSS (model group), and these reduced to 26%, 10% and 5% in AP (1.25%, 2.5% and 5%) treatment group respectively. Western blot analysis demonstrated that TLR4 (membrane protein), MyD88, NF-��B p65 (nuclear protein) expression decreased significantly at protein level; and the secretion of TNF-�� decreased in control group(P<0.05). CONCLUSION AP could protect ICR mice from CACC effectively and the possible mechanism may be related to the inhibition of TLR4/MyD88/ NF-��B pathways.
�ŵ�,������,����,����,���,����,����,÷���. ƻ������Ԥ��С��᳦�װ�������ü�������о�[J]. �й�ҩѧ��־, 2015, 50(17): 1527-1531.
ZHANG Dian,WANG Fen-xia, MI Man, SUN Yang ,LI Yu-hua, FAN Lei, LIU Li, MEI Qi-bing. Effect and Mechanism of Apple Polysaccharides on Experimental Colitis Associated Colorectal Cancer in Mice. Chinese Pharmaceutical Journal, 2015, 50(17): 1527-1531.
MISALE S, YAEGER R, HOBOR S, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer[J]. Nature, 2012, 486(7404):532-536.
[2]
AVIELLO G, CORR S C, JOHNSTON D G, et al. MyD88 Adaptor-like (Mal) regulates intestinal homeostasis and colitis-associated colorectal cancer in mice[J]. Am J Physiol Gastrointest Liver Physiol, 2014, 306(9):769-778.
[3]
JAGANATHAN S K, VELLAYAPPAN M V, NARASIMHAN G, et al. Role of pomegranate and citrus fruit juices in colon cancer prevention [J]. World J Gastroenterol, 2014, 20(16):4618-4625.
[4]
GROSSO G, BIONDI A, GALVANO F, et al. Factors associated with colorectal cancer in the context of the mediterranean diet:A case-control study [J]. Nutr Cancer, 2014, 66(4):558-565.
[5]
LI Y, LIU L, NIU Y, et al. Modified apple polysaccharide prevents against tumorigenesis in a mouse model of colitis-associated colon cancer:Role of galectin-3 and apoptosis in cancer prevention[J]. Eur J Nutr, 2012,51(1):107-117.
[6]
LI Y, NIU Y, MEI Q, et al. Modified apple polysaccharides could induce apoptosis in colorectal cancer cells [J]. J Food Sci, 2010, 75 (8):224-229.
[7]
TANAKA T, KOHNO H, SUZUKI R, et al. A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate [J]. Cancer Sci,2003, 94(11):965-973.
[8]
FUKATA M, CHEN A, KLEPPER A, et al. Cox-2 is regulated by Toll-like receptor-4 (TLR4) signaling:Role in proliferation and apoptosis in the intestine[J]. Gastroenterology, 2006, 131(3):862-877.
[9]
LI Y,LIU L,NIU Y, et al. Modified apple polysaccharide prevents against tumorigenesis in a mouse model of colitis-associated colon cancer:Role of galectin-3 and apoptosis in cancer prevention[J]. Eur J Nutr,2012 ,51(1):107-117.
[10]
NIELSEN O H, JESS T, BJERRUM J T, et al. Ulcerative colitis[J]. Ugeskr Laeger, 2013, 175(20):1412-1416.
[11]
VIENNOIS E, CHEN F, MERLIN D. NF-��B Pathway in colitis-associated cancers[J]. Transl Gastrointest Cancer, 2013, 2(1):21-29.
[12]
SZUMILAS D, KRYSIAK R, OKOPIE�� B. The role of TLR4 receptor in development of inflammation and carcinogenesis in ulcerative colitis and pharmacotherapy of this disorder [J]. Wiad Lek,2013, 66(1):3-9.
[13]
SLATTERY M L, HERRICK J S, BONDURANT K L, et al. Toll-like receptor genes and their association with colon and rectal cancer development and prognosis [J]. Int J Cancer, 2012, 130(12):2974-2980.
[14]
CAO H, XU Z, LONG H, et al. The-765C allele of the cyclooxygenase-2 gene as a potential risk factor of colorectal cancer:A meta-analysis[J]. Tohoku J Exp Med, 2010, 222(1):15-21.
[15]
UMESALMA S, SUDHANDIRAN G. Differential inhibitory effects of the polyphenol ellagic acid on inflammatory mediators NF-kappaB, iNOS, COX-2, TNF-alpha, and IL-6 in 1,2-dimethylhydrazine-induced rat colon carcinogenesis [J]. Basic Clin Pharmacol Toxicol, 2010, 107(2):650-655.