Effects of DNA Methyltransferase Inhibitors and Histone Deacetylase Inhibitors on Expression of E-cadherin and Invasion of Cholangiocarcinoma Cell_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Hong , SHU Yi , CHEN Yongjun , ZOU Shengquan

* Department of Biliary and Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College， Huazhong University of Science and Technology, Wuhan 430030, ChinaCorresponding Author: ZOU Sheng-quan, E-mail: sqzou05@yahoo.com.cn;

Corresponding author：

Keywords：

DNA methyltransferase inhibitor; Histone deacetylase inhibitor; DNA methylation

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Objective To investigate the effects of DNA methyltransferase inhibitor (DNMTi) and histone deacetylase inhibitor (HDCAi) on expression of E-cadherin gene and invasiveness of cholangiocarcinoma cell. Methods According to different treatment, the QBC939 cells were divided into four groups: blank control group, hydralazine group, valproic acid group and hydralazine and valproic acid combined group. After 48 h, the expression of E-cadherin was evaluated by reverse transcription-PCR (RT-PCR), mehtylation specific PCR (MSP) and Western blot, the invasiveness of QBC939 cells was evaluated by Transwell method. Results There was no expression of E-cadherin mRNA and protien in blank control group and valproic acid group. The expressions of E-cadherin mRNA and protien in hydralazine and valproic acid combined group were higher than those in hydralazine group ( P ＜ 0.01), while the invasiveness of QBC939 cells of hydralazine and valproic acid combined group was much lower than that of blank control group, hydralazine group and valproic acid group ( P ＜ 0.01). Conclusion DNMTi and HDACi can synergistically re-express E-cadherin gene and weaken the invasiveness of QBC939 cell, which plays an important part in treatment of cholangiocarcinoma.

Citation： LI Hong,SHU Yi,CHEN Yongjun,ZOU Shengquan,.. Effects of DNA Methyltransferase Inhibitors and Histone Deacetylase Inhibitors on Expression of E-cadherin and Invasion of Cholangiocarcinoma Cell. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(1): 44-47. doi: Copy

1.	8 de la Cruz-Hernández E, Pérez-Cárdenas E, Contreras-Paredes A, et al . The effects of DNA methylation and histone deacetylase inhibitors on human papillomavirus early gene expression in cervical cancer, an in vitro and clinical study [Ｊ] . Virol J, 2007; 4： 18 9 Herman JG, Graff JR, Myhnen S, et al . Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands [Ｊ] . Proc Natl Acad Sci USA, 1996; 93(18)： 9821.
2.	Berx G, Cleton-Jansen AM, Nollet F, et al . E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers [Ｊ] . EMBO J, 1995; 14(24)： 6107.
3.	李强，王剑明，刘聪，等. aPKC-ι和E-cadherin 在胆管癌组织中的表达及意义 [Ｊ] . 癌症， 2007； 26(7)： 715.
4.	Yang B, House MG, Guo M, et al . Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma [Ｊ] . Mod Pathol, 2005; 18(3)： 412.
5.	Santini V, Kantarjian HM, Issa JP. Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications [Ｊ] . Ann Intern Med, 2001; 134(7)： 573.
6.	Zhu WG, Otterson GA. The interaction of histone deacetylase inhibitors and DNA methyltransferase inhibitors in the treatment of human cancer cells [Ｊ] . Curr Med Chem Anticancer Agents, 2003; 3(3)： 187.
7.	Segura-Pacheco B, Trejo-Becerril C, Perez-Cardenas E, et al . Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy [Ｊ] . Clin Cancer Res, 2003; 9(5)： 1596.
8.	Chavez-Blanco A, Perez-Plasencia C, Perez-Cardenas E, et al . Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacety lase inhibitor valproic acid in cancer cell lines [Ｊ] . Cancer Cell Int, 2006; 6： 2.
9.	Vleminckx K, Vakaet L Jr, Mareel M, et al . Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role [Ｊ] . Cell, 1991; 66(1)： 107.
10.	车向明，王曙逢，樊林，等. E-cadherin反义寡核苷酸对肿瘤细胞浸润能力影响的研究 [Ｊ] . 中国普外基础与临床杂志， 2006； 13(2)： 191.
11.	Hirohashi S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers [Ｊ] . Am J Pathol, 1998; 153 (2)： 333.
12.	Mareel M, Bracke M, van Roy F. Cancer metastasis: negative regulation by an invasion-suppressor complex [Ｊ] . Cancer Detect Prev, 1995; 19(5)： 451.
13.	邹声泉. 胆管癌外科治疗的现状与展望 [Ｊ] . 中国普外基础与临床杂志， 2008； 15(2)： 77.
14.	李哲夫，史光军. 胆管癌的基因表达及其临床意义 [Ｊ] . 中国普外基础与临床杂志， 2000； 7(2)： 131.
15.	Mikami T, Saegusa M, Mitomi H, et al . Significant correlations of E-cadherin, catenin, and CD44 variant form expression with carcinoma cell differentiation and prognosis of extrahepatic bile duct carcinomas [Ｊ] . Am J Clin Pathol, 2001; 116(3)： 369.
16.	Asayama Y, Taguchi Ki K, Aishima Si S, et al . The mode of tumour progression in combined hepatocellular carcinoma and cholangiocarcinoma: an immunohistochemical analysis of E-cadherin, alpha-catenin and beta-catenin [Ｊ] . Liver, 2002; 22 (1)： 43.
17.	Sharma D, Blum J, Yang X, et al . Release of methyl CpG binding proteins and histone deacetylase 1 from the Estrogen receptor alpha (ER) promoter upon reactivation in ER-negative human breast cancer cells [Ｊ] . Mol Endocrinol, 2005; 19(7)： 1740.
18.	El-Osta A, Kantharidis P, Zalcberg JR, et al . Precipitous release of methyl-CpG binding protein 2 and histone deacetylase 1 from the methylated human multidrug resistance gene (MDR1) on activation [Ｊ] . Mol Cell Biol, 2002; 22(6)： 1844.
19.	Zhang Y, Fatima N, Dufau ML. Coordinated changes in DNA methylation and histone modifications regulate silencing/derepression of luteinizing hormone receptor gene transcription [Ｊ] . Mol Cell Biol, 2005; 25(18)： 7929.

1. 8 de la Cruz-Hernández E, Pérez-Cárdenas E, Contreras-Paredes A, et al . The effects of DNA methylation and histone deacetylase inhibitors on human papillomavirus early gene expression in cervical cancer, an in vitro and clinical study [Ｊ] . Virol J, 2007; 4： 18 9 Herman JG, Graff JR, Myhnen S, et al . Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands [Ｊ] . Proc Natl Acad Sci USA, 1996; 93(18)： 9821.
2. Berx G, Cleton-Jansen AM, Nollet F, et al . E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers [Ｊ] . EMBO J, 1995; 14(24)： 6107.
3. 李强，王剑明，刘聪，等. aPKC-ι和E-cadherin 在胆管癌组织中的表达及意义 [Ｊ] . 癌症， 2007； 26(7)： 715.
4. Yang B, House MG, Guo M, et al . Promoter methylation profiles of tumor suppressor genes in intrahepatic and extrahepatic cholangiocarcinoma [Ｊ] . Mod Pathol, 2005; 18(3)： 412.
5. Santini V, Kantarjian HM, Issa JP. Changes in DNA methylation in neoplasia: pathophysiology and therapeutic implications [Ｊ] . Ann Intern Med, 2001; 134(7)： 573.
6. Zhu WG, Otterson GA. The interaction of histone deacetylase inhibitors and DNA methyltransferase inhibitors in the treatment of human cancer cells [Ｊ] . Curr Med Chem Anticancer Agents, 2003; 3(3)： 187.
7. Segura-Pacheco B, Trejo-Becerril C, Perez-Cardenas E, et al . Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy [Ｊ] . Clin Cancer Res, 2003; 9(5)： 1596.
8. Chavez-Blanco A, Perez-Plasencia C, Perez-Cardenas E, et al . Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacety lase inhibitor valproic acid in cancer cell lines [Ｊ] . Cancer Cell Int, 2006; 6： 2.
9. Vleminckx K, Vakaet L Jr, Mareel M, et al . Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role [Ｊ] . Cell, 1991; 66(1)： 107.
10. 车向明，王曙逢，樊林，等. E-cadherin反义寡核苷酸对肿瘤细胞浸润能力影响的研究 [Ｊ] . 中国普外基础与临床杂志， 2006； 13(2)： 191.
11. Hirohashi S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers [Ｊ] . Am J Pathol, 1998; 153 (2)： 333.
12. Mareel M, Bracke M, van Roy F. Cancer metastasis: negative regulation by an invasion-suppressor complex [Ｊ] . Cancer Detect Prev, 1995; 19(5)： 451.
13. 邹声泉. 胆管癌外科治疗的现状与展望 [Ｊ] . 中国普外基础与临床杂志， 2008； 15(2)： 77.
14. 李哲夫，史光军. 胆管癌的基因表达及其临床意义 [Ｊ] . 中国普外基础与临床杂志， 2000； 7(2)： 131.
15. Mikami T, Saegusa M, Mitomi H, et al . Significant correlations of E-cadherin, catenin, and CD44 variant form expression with carcinoma cell differentiation and prognosis of extrahepatic bile duct carcinomas [Ｊ] . Am J Clin Pathol, 2001; 116(3)： 369.
16. Asayama Y, Taguchi Ki K, Aishima Si S, et al . The mode of tumour progression in combined hepatocellular carcinoma and cholangiocarcinoma: an immunohistochemical analysis of E-cadherin, alpha-catenin and beta-catenin [Ｊ] . Liver, 2002; 22 (1)： 43.
17. Sharma D, Blum J, Yang X, et al . Release of methyl CpG binding proteins and histone deacetylase 1 from the Estrogen receptor alpha (ER) promoter upon reactivation in ER-negative human breast cancer cells [Ｊ] . Mol Endocrinol, 2005; 19(7)： 1740.
18. El-Osta A, Kantharidis P, Zalcberg JR, et al . Precipitous release of methyl-CpG binding protein 2 and histone deacetylase 1 from the methylated human multidrug resistance gene (MDR1) on activation [Ｊ] . Mol Cell Biol, 2002; 22(6)： 1844.
19. Zhang Y, Fatima N, Dufau ML. Coordinated changes in DNA methylation and histone modifications regulate silencing/derepression of luteinizing hormone receptor gene transcription [Ｊ] . Mol Cell Biol, 2005; 25(18)： 7929.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of DNA Methyltransferase Inhibitors and Histone Deacetylase Inhibitors on Expression of E-cadherin and Invasion of Cholangiocarcinoma Cell

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