Influence of Neotype Matrix Metalloproteinase Inhibitor LY52 on Matrix Metalloproteinase Expression and Invasion in Vitro of Hepatocellular Carcinoma Cell Line_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHAO Xin ^1,2 , XU Huanli ³ , TANG Wei ³ , KOKUDO Norihiro ³ , DONG Jiahong ¹

1.Department of Hepatobiliary Surgery, The Chinese PLA General Hospital, Beijing 100853, China;;
2.Department of Hepatobiliary Surgery, The No.302 Hospital of PLA, Beijing 100039, China;;
3.HepatoBiliaryPancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 1138655, Japan;

Corresponding author：

Keywords：

LY52; Hepatocellular carcinoma; Matrix metalloproteinases; Invasion

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Abstract Full text Figures/Tables Video References Cited by

Objective To examine the effects of newly designed LY52 on the expression of matrix metalloproteinases and invasive ability of hepatocellular carcinoma HepG2 cells.
Methods The effects of LY52 on the proliferations of HepG2 cells were detected by MTT assay. Gelatin zymography and Western blot were used to detect the effects of LY52 on matrix metalloproteinase-2 expression in the cell line. Transwell chamber assay was used to detect the effects of LY52 on the invasion of the cells. Results No obvious inhibitory or cytotoxicity effects of LY52 was found in lower concentrations ( lt;200 μg/ml) of LY52. Gelatin zymography and Western blot showed that matrix metalloproteinase-2 expression were inhibited by LY52 in a dose-dependent manner in HepG2 cells. Furthermore, transwell chamber assay showed that LY52 could significantly inhibit the invasion of the cell line in a dose-dependent manner.
Conclusion The results suggest that LY52 may inhibit the invasion of hepatocellular carcinoma cells by suppressing the matrix metalloproteinase-2 activity.

Citation： ZHAO Xin ,XU Huanli,TANG Wei,KOKUDO Norihiro,DONG Jiahong. Influence of Neotype Matrix Metalloproteinase Inhibitor LY52 on Matrix Metalloproteinase Expression and Invasion in Vitro of Hepatocellular Carcinoma Cell Line. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(8): 798-802. doi: Copy

1.	Mtt M, Soini Y, Liakka A, et al. Differential expression of matrix metalloproteinase (MMP)2, MMP9, and membrane type 1MMP in hepatocellular and pancreatic adenocarcinoma: implications for tumor progression and clinical prognosis [J]. Clin Cancer Res， 2000； 6(7): 27262734.
2.	Yamamoto H, Itoh F, Adachi Y, et al. Relation of enhanced secretion of active matrix metalloproteinases with tumor spread in human hepatocellular carcinoma [J]. Gastroenterology， 1997； 112(4): 12901296.
3.	Rossello A, Nuti E, Orlandini E, et al. New NarylsulfonylNalkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase A (MMP2) [J]. Bioorg Med Chem， 2004; 12(9): 24412450.
4.	Levitt NC, Eskens FA, O’Byrne KJ, et al. Phase Ⅰ and pharmacological study of the oral matrix metalloproteinase inhibitor, MMI270 (CGS27023A), in patients with advanced solid cancer [J]. Clin Cancer Res, 2001; 7(7): 19121922.
5.	Li YL, Xu WF. Design, synthesis, and activity of caffeoyl pyrrolidine derivatives as potential gelatinase inhibitors [J]. Bioorg Med Chem， 2004; 12(19): 51715180.
6.	Li X, Li Y, Xu W. Design, synthesis, and evaluation of novel galloyl pyrrolidine derivatives as potential antitumor agents [J]. Bioorg Med Chem， 2006; 14(5): 12871293.
7.	Qu XJ, Yuan YX, Tian ZG, et al. Using caffeoyl pyrrolidine derivative LY52, a potential inhibitor of matrix metalloproteinase2, to suppress tumor invasion and metastasis [J]. Int J Mol Med， 2006; 18(4): 609614.
8.	吴立刚，刘奇伦，胡志强. MMP2和VEGFC在甲状腺乳头状癌中的表达及临床意义 [J]. 中国普外基础与临床杂志，2009; 16(11): 906910.
9.	王鹏，郭琳，王强. PTEN、Fas/FasL和MMP2在胃癌组织的表达及其临床意义 [J]. 中国普外基础与临床杂志， 2009; 16(12): 991995.
10.	Deryugina EI, Quigley JP. Matrix metalloproteinases and tumor metastasis [J]. Cancer Metastasis Rev, 2006; 25(1): 934.
11.	Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations [J]. Science, 2002; 295(5564): 23872392.
12.	赵新，丛文铭，谭璐，等. MMP2和TIMP2在肝癌中的表达及其意义 [J]. 临床肿瘤学杂志， 2001; 6(1): 912.
13.	刘智敏，严律南，汤宇，等. 血管内皮生长因子和基质金属蛋白酶9在肝细胞癌中的表达及其意义 [J]. 中国普外基础与临床杂志， 2002; 9(6): 421423.
14.	Sakamoto Y, Mafune K, Mori M, et al. Overexpression of MMP9 correlates with growth of small hepatocellular carcinoma [J]. Int J Oncol， 2000; 17(2): 237243.

1. Mtt M, Soini Y, Liakka A, et al. Differential expression of matrix metalloproteinase (MMP)2, MMP9, and membrane type 1MMP in hepatocellular and pancreatic adenocarcinoma: implications for tumor progression and clinical prognosis [J]. Clin Cancer Res， 2000； 6(7): 27262734.
2. Yamamoto H, Itoh F, Adachi Y, et al. Relation of enhanced secretion of active matrix metalloproteinases with tumor spread in human hepatocellular carcinoma [J]. Gastroenterology， 1997； 112(4): 12901296.
3. Rossello A, Nuti E, Orlandini E, et al. New NarylsulfonylNalkoxyaminoacetohydroxamic acids as selective inhibitors of gelatinase A (MMP2) [J]. Bioorg Med Chem， 2004; 12(9): 24412450.
4. Levitt NC, Eskens FA, O’Byrne KJ, et al. Phase Ⅰ and pharmacological study of the oral matrix metalloproteinase inhibitor, MMI270 (CGS27023A), in patients with advanced solid cancer [J]. Clin Cancer Res, 2001; 7(7): 19121922.
5. Li YL, Xu WF. Design, synthesis, and activity of caffeoyl pyrrolidine derivatives as potential gelatinase inhibitors [J]. Bioorg Med Chem， 2004; 12(19): 51715180.
6. Li X, Li Y, Xu W. Design, synthesis, and evaluation of novel galloyl pyrrolidine derivatives as potential antitumor agents [J]. Bioorg Med Chem， 2006; 14(5): 12871293.
7. Qu XJ, Yuan YX, Tian ZG, et al. Using caffeoyl pyrrolidine derivative LY52, a potential inhibitor of matrix metalloproteinase2, to suppress tumor invasion and metastasis [J]. Int J Mol Med， 2006; 18(4): 609614.
8. 吴立刚，刘奇伦，胡志强. MMP2和VEGFC在甲状腺乳头状癌中的表达及临床意义 [J]. 中国普外基础与临床杂志，2009; 16(11): 906910.
9. 王鹏，郭琳，王强. PTEN、Fas/FasL和MMP2在胃癌组织的表达及其临床意义 [J]. 中国普外基础与临床杂志， 2009; 16(12): 991995.
10. Deryugina EI, Quigley JP. Matrix metalloproteinases and tumor metastasis [J]. Cancer Metastasis Rev, 2006; 25(1): 934.
11. Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: trials and tribulations [J]. Science, 2002; 295(5564): 23872392.
12. 赵新，丛文铭，谭璐，等. MMP2和TIMP2在肝癌中的表达及其意义 [J]. 临床肿瘤学杂志， 2001; 6(1): 912.
13. 刘智敏，严律南，汤宇，等. 血管内皮生长因子和基质金属蛋白酶9在肝细胞癌中的表达及其意义 [J]. 中国普外基础与临床杂志， 2002; 9(6): 421423.
14. Sakamoto Y, Mafune K, Mori M, et al. Overexpression of MMP9 correlates with growth of small hepatocellular carcinoma [J]. Int J Oncol， 2000; 17(2): 237243.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Influence of Neotype Matrix Metalloproteinase Inhibitor LY52 on Matrix Metalloproteinase Expression and Invasion in Vitro of Hepatocellular Carcinoma Cell Line

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