Activation of Farnesiod X Receptor Inhibited The Growth of Colon Cancer Cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 ZHUSong-ming , ZHANGChao-feng , ZHANGJie , DAIGang , HUANGXia

Department of General Surgery, Xinhua Hospital Chongming Branch, Shanghai Jiaotong University School of Medicine, Shanghai 202150, China;

Corresponding author：

ZHUSong-ming, Email: peaker2005@sina.com

Keywords：

Colon cancer; Farnesiod X receptor; Farnesoid X receptor agonist

DOI：

10.7507/1007-9424.20140197

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effects of specific farnesiod X receptor(FXR) agonist on growth of colon cancer cells in vitro. Methods The effects of specific FXR agonist(GW4064) on the growth of HCT116 cells of colon cancer were studied in vitro by using MTT and flow cytometry. The mRNA expressions of FXR and vascular endothelial grouth factor(VEGF), were determined by using RT-PCR. Results The FXR specific agonist GW4064 could increase the FXR mRNA expression of HCT-116 cells of colon cancer, downregulation of VEGF mRNA expression, and had obvious inhibitory effect on growth of HCT-116 cells, and promoted the apoptosis of HCT116 cells in a dose and time dependence. Conclusions GW4064 can significantly inhibit colon cancer cells in vitro. FXR may be a potential treatment arget of colon cancer.

Citation： ZHUSong-ming, ZHANGChao-feng, ZHANGJie, DAIGang, HUANGXia. Activation of Farnesiod X Receptor Inhibited The Growth of Colon Cancer Cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(7): 827-831. doi: 10.7507/1007-9424.20140197 Copy

1.	Ajouz H, Mukherji D, Shamseddine A. Secondary bile acids: an underrecognized cause of colon cancer[J]. World J Surg Oncol, 2014, 12(1):164.
2.	Hofmanová J, Straková N, Vaculová AH, et al. Interaction of dietary fatty acids with tumour necrosis factor family cytokines during colon inflammation and cancer[J]. Mediators Inflamm, 2014, 2014:848632.
3.	Debruyne PR, Bruyneel EA, Li X, et al. The role of bile acids in carcinogenesis[J]. Mutat Res, 2001, 480-481:359-369.
4.	Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90.
5.	中华人民共和国卫生部. 2011年中国卫生统计提要[EB/OL]. www. moh. gov. cn. 2011-05-27.
6.	Yang F, Huang X, Yi T, et al. Spontaneous development of liver tumors in the absence of the bile acid receptor farnesiod X receptor[J]. Cancer Res, 2007, 67(3):863-867.
7.	Kim I, Morimura K, Shah Y, et al. Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice[J]. Carcinogenesis, 2007, 28(5):940-946.
8.	Maran RR, Thomas A, Roth M, et al. Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development[J]. J Pharmacol Exp Ther, 2009, 328(2):469-477.
9.	Koutsounas I, Giaginis C, Theocharis S. Farnesoid X receptor (FXR) from normal to malignant state[J]. Histol Histopathol, 2012, 27(7):835-853.
10.	Wang YD, Chen WD, Wang M, et al. Farnesoid X receptor antagonizes nuclear factor kappaB in hepatic inflammatory response[J]. Hepatology, 2008, 48(5):1632-1643.
11.	Modica S, Murzilli S, Salvatore L, et al. Nuclear bile acid receptor FXR protects against intestinal tumorigenesis[J]. Cancer Res, 2008, 68(23):9589-9594.
12.	Kim MS, Shigenaga J, Moser A, et al. Repression of farnesoid X receptor during the acute phase response[J]. J Biol Chem, 2003, 278(11):8988-8995.
13.	De Gottardi A, Touri F, Maurer CA, et al. The bile acid nuclear receptor FXR and the bile acid binding protein IBABP are differently expressed in colon cancer[J]. Dig Dis Sci, 2004, 49(6): 982-989.
14.	Torres J, Bao X, Iuga AC, et al. Farnesoid X receptor expression is decreased in colonic mucosa of patients with primary sclerosing cholangitis and colitis-associated neoplasia[J]. Inflamm Bowel Dis, 2013, 19(2):275-282.
15.	Lax S, Schauer G, Prein K, et al. Expression of the nuclear bile acid receptor/farnesoid X receptor is reducedin human colon carcinoma compared to nonneoplastic mucosa independent from siteand may be associated with adverse prognosis[J]. Int J Cancer, 2012, 130(10):2232-2239.
16.	张超峰, 王坚.法尼酯X受体在胆管癌中表达特点[J].外科理论与实践, 2009, 14(2):171-173.
17.	Swales KE, Korbonits M, Carpenter R, et al. The farnesiod X receptor is expressed in breast cancer and regulates apoptosis and aromatase expression[J]. Cancer Res, 2006, 66(20):10120-10126.
18.	Smith DL, Keshavan P, Avissar U, et al. Sodium taurocholate inhibits intestinal adenoma formation in APCMin/+mice, potentially through activation of the farnesoid X receptor[J]. Carcinogenesis, 2010, 31(6):1100-1109.
19.	丁晖, 潘运龙, 覃莉, 等.结肠癌VEGF、p53和CerbB-2蛋白联合表达与肝肺转移的关系[J].实用医学杂志, 2011, 27(9): 1593-1595.
20.	Li YT, Swales KE, Thomas GJ, et al. Farnesoid X receptor ligands inhibit vascular smooth muscle cell inflammation and migration[J]. Arterioscler Thromb Vasc Biol, 2007, 27(12): 2606-2611.
21.	Peng Z, Raufman JP, Xie G. Src-mediated cross-talk between farnesoid X and epidermal growth factor receptors inhibits human intestinal cell proliferation and tumorigenesis[J]. PLoS One, 2012, 7(10):e48461.
22.	Bailey AM, Zhan L, Maru D, et al. FXR silencing in human colon cancer by DNA methylation and KRAS signaling[J]. Am J Physiol Gastrointest Liver Physiol, 2014, 306(1):G48-G58.
23.	Zimber A, Gespach C. Bile acids and derivatives, their nuclear receptors FXR, PXR and ligands:role in health and disease and their therapeutic potential[J]. Anticancer Agents Med Chem, 2008, 8(5):540-563.
24.	Lew JL, Zhao A, Yu J, et al. The farnesoid X receptor controls gene expression in a ligand-and promoter-selective fashion[J]. J Biol Chem, 2004, 279(10):8856-8861.
25.	Modica S, Moschetta A. Nuclear bile acid receptor FXR as pharmacological target:are we there yet?[J]. FEBS Letters, 2006, 580(23):5492-5499.

1. Ajouz H, Mukherji D, Shamseddine A. Secondary bile acids: an underrecognized cause of colon cancer[J]. World J Surg Oncol, 2014, 12(1):164.
2. Hofmanová J, Straková N, Vaculová AH, et al. Interaction of dietary fatty acids with tumour necrosis factor family cytokines during colon inflammation and cancer[J]. Mediators Inflamm, 2014, 2014:848632.
3. Debruyne PR, Bruyneel EA, Li X, et al. The role of bile acids in carcinogenesis[J]. Mutat Res, 2001, 480-481:359-369.
4. Jemal A, Bray F, Center MM, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2):69-90.
5. 中华人民共和国卫生部. 2011年中国卫生统计提要[EB/OL]. www. moh. gov. cn. 2011-05-27.
6. Yang F, Huang X, Yi T, et al. Spontaneous development of liver tumors in the absence of the bile acid receptor farnesiod X receptor[J]. Cancer Res, 2007, 67(3):863-867.
7. Kim I, Morimura K, Shah Y, et al. Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice[J]. Carcinogenesis, 2007, 28(5):940-946.
8. Maran RR, Thomas A, Roth M, et al. Farnesoid X receptor deficiency in mice leads to increased intestinal epithelial cell proliferation and tumor development[J]. J Pharmacol Exp Ther, 2009, 328(2):469-477.
9. Koutsounas I, Giaginis C, Theocharis S. Farnesoid X receptor (FXR) from normal to malignant state[J]. Histol Histopathol, 2012, 27(7):835-853.
10. Wang YD, Chen WD, Wang M, et al. Farnesoid X receptor antagonizes nuclear factor kappaB in hepatic inflammatory response[J]. Hepatology, 2008, 48(5):1632-1643.
11. Modica S, Murzilli S, Salvatore L, et al. Nuclear bile acid receptor FXR protects against intestinal tumorigenesis[J]. Cancer Res, 2008, 68(23):9589-9594.
12. Kim MS, Shigenaga J, Moser A, et al. Repression of farnesoid X receptor during the acute phase response[J]. J Biol Chem, 2003, 278(11):8988-8995.
13. De Gottardi A, Touri F, Maurer CA, et al. The bile acid nuclear receptor FXR and the bile acid binding protein IBABP are differently expressed in colon cancer[J]. Dig Dis Sci, 2004, 49(6): 982-989.
14. Torres J, Bao X, Iuga AC, et al. Farnesoid X receptor expression is decreased in colonic mucosa of patients with primary sclerosing cholangitis and colitis-associated neoplasia[J]. Inflamm Bowel Dis, 2013, 19(2):275-282.
15. Lax S, Schauer G, Prein K, et al. Expression of the nuclear bile acid receptor/farnesoid X receptor is reducedin human colon carcinoma compared to nonneoplastic mucosa independent from siteand may be associated with adverse prognosis[J]. Int J Cancer, 2012, 130(10):2232-2239.
16. 张超峰, 王坚.法尼酯X受体在胆管癌中表达特点[J].外科理论与实践, 2009, 14(2):171-173.
17. Swales KE, Korbonits M, Carpenter R, et al. The farnesiod X receptor is expressed in breast cancer and regulates apoptosis and aromatase expression[J]. Cancer Res, 2006, 66(20):10120-10126.
18. Smith DL, Keshavan P, Avissar U, et al. Sodium taurocholate inhibits intestinal adenoma formation in APCMin/+mice, potentially through activation of the farnesoid X receptor[J]. Carcinogenesis, 2010, 31(6):1100-1109.
19. 丁晖, 潘运龙, 覃莉, 等.结肠癌VEGF、p53和CerbB-2蛋白联合表达与肝肺转移的关系[J].实用医学杂志, 2011, 27(9): 1593-1595.
20. Li YT, Swales KE, Thomas GJ, et al. Farnesoid X receptor ligands inhibit vascular smooth muscle cell inflammation and migration[J]. Arterioscler Thromb Vasc Biol, 2007, 27(12): 2606-2611.
21. Peng Z, Raufman JP, Xie G. Src-mediated cross-talk between farnesoid X and epidermal growth factor receptors inhibits human intestinal cell proliferation and tumorigenesis[J]. PLoS One, 2012, 7(10):e48461.
22. Bailey AM, Zhan L, Maru D, et al. FXR silencing in human colon cancer by DNA methylation and KRAS signaling[J]. Am J Physiol Gastrointest Liver Physiol, 2014, 306(1):G48-G58.
23. Zimber A, Gespach C. Bile acids and derivatives, their nuclear receptors FXR, PXR and ligands:role in health and disease and their therapeutic potential[J]. Anticancer Agents Med Chem, 2008, 8(5):540-563.
24. Lew JL, Zhao A, Yu J, et al. The farnesoid X receptor controls gene expression in a ligand-and promoter-selective fashion[J]. J Biol Chem, 2004, 279(10):8856-8861.
25. Modica S, Moschetta A. Nuclear bile acid receptor FXR as pharmacological target:are we there yet?[J]. FEBS Letters, 2006, 580(23):5492-5499.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Activation of Farnesiod X Receptor Inhibited The Growth of Colon Cancer Cells

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