Effect of ZnPP Ⅸ on HO-1 and GST-π Expressions and Chemosensitivity of Drug-Resistant Hepatic Carcinoma Cell Line Bel/Fu_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Junkai , WANG Zhongyu , GONG Peng , LUO Haifeng , CHENG Lei.

Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China;

Corresponding author：

Keywords：

Chemotherapy resistance; Hepatic carcinoma cell; Glutathione-S-transferase-π; Heme oxygenase-1; ZnPP Ⅸ

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

ObjectiveTo evaluate the effect of ZnPP Ⅸ on the expressions of heme oxygenase-1 (HO-1) and glutathione-Stransferase-π （GST-π） and the chemosensitivity of drug-resistant hepatic carcinoma cell line Bel/Fu, and explore it’s possibility to reverse drug-resistance and the relevant regulating mechanism. Methods①MTT assay was adopted to detect the drug sensitivity for adriamycin, mitomycin, and 5-fluorouracil of Bel/Fu cell after ZnPP Ⅸ being induced for 24 h. ②RTPCR was carried out to detect the expressions of HO-1 and GST-π mRNA after Bel/FU cells being treated with different concentrations ZnPP Ⅸ for 24 h. ResultsAfter Bel/Fu cells being treated with ZnPP Ⅸ for 24 h, the 50% inhibiting concentration (IC50) for drugs was decreased dramatically （P lt;0.05）. Meanwhile, the expressions of HO-1 and GST-π mRNA in the treated cells also decreased dose-dependently (P lt;0.01). ConclusionsZnPP Ⅸ can increase the chemosensitivity of Bel/FU cells by down-regulation of HO-1 and GST-π expression. ZnPP Ⅸ is a potential agent to reverse multidrug resistance of hepatic carcinoma cells.

Citation： ZHANG Junkai,WANG Zhongyu,GONG Peng,LUO Haifeng,CHENG Lei.. Effect of ZnPP Ⅸ on HO-1 and GST-π Expressions and Chemosensitivity of Drug-Resistant Hepatic Carcinoma Cell Line Bel/Fu. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(5): 503-506. doi: Copy

1.	Motterlini R, Foresti R, Bassi R, et al. Endothelial heme oxygenase1 induction by hypoxia. Modulation by inducible nitricoxide synthase and Snitrosothiols [J]. J Biol Chem, 2000, 275(18): 1361313620.
2.	Goodman AI, Choudhury M, da Silva JL, et al. Overexpression of the heme oxygenase gene in renal cell carcinoma [J]. Proc Soc Exp Biol Med, 1997, 214(1): 5461.
3.	Maines MD, Abrahamsson PA.Expression of heme oxygenase1 (HSP32) in human prostate: normal, hyperplastic, and tumor tissue distribution [J]. Urology, 1996, 47(5): 727733.
4.	Reiter TA, Demple B. Carbon monoxide mediates protection against nitric oxide toxicity in HeLa cells [J]. Free Radic Biol Med, 2005, 39(8): 10751088.
5.	Wagener FA, da Silva JL, Farley T, et al. Differential effects of heme oxygenase isoforms on heme mediation of endothelial intracellular adhesion molecule 1 expression [J]. J Pharmacol Exp Ther， 1999， 291(1): 416423.
6.	张黎, 程力, 李更生, 等. 血红素氧化酶1在大鼠肝移植中保护作用的研究 [J]. 中国普外基础与临床杂志, 2008, 15(9): 665 670.
7.	CordonCardo C, O’Brien JP, Boccia J, et al. Expression of the multidrug resistance gene product (Pglycoprotein) in human normal and tumor tissues [J]. J Histochem Cytochem, 1990, 38(9): 12771287.
8.	魏学明, 顾国利, 任力, 等. 多药耐药基因产物在胃癌组织中的表达及意义 [J]. 中国普外基础与临床杂志, 2009, 16(12): 10001004.
9.	Berberat PO, Dambrauskas Z, Gulbinas A, et al. Inhibition of heme oxygenase1 increases responsiveness of pancreatic cancer cells to anticancer treatment [J]. Clin Cancer Res, 2005, 11(10): 37903798．.
10.	张隽开, 王忠裕, 丁大鹏，等. 血红素加氧酶对肝癌耐药细胞株Bel/Fu化疗敏感性的影响 [J]. 中华肿瘤防治杂志, 2009, 16(13): 990993．.
11.	Yu DS, Lin JC, Hsieh DS, et al. Modulation of MDR1 gene by MIF and GSTpi with drug resistance generation in hormone independent prostate cancer [J]. Arch Androl, 2006, 52(4): 283291.
12.	薛军, 支学军, 屈明, 等. 胃癌及食管癌中肿瘤耐药标志物P糖蛋白和谷胱甘肽转移酶表达的研究 [J]. 中国普外基础与临床杂志, 2002, 9(5): F2.
13.	Dirven HA, Dictus EL, Broeders NL, et al. The role of human glutathione Stransferase isoenzymes in the formation of glutathione conjugates of the alkylating cytostatic drug thiotepa [J]. Cancer Res, 1995, 55(8): 17011706.
14.	Kuroda H, Sugimoto T, Ueda K, et al. Different drug sensitivity in two neuroblastoma cell lines established from the same patient before and after chemotherapy [J]. Int J Cancer, 1991, 47(5): 732737.
15.	Sato K, Satoh K, Tsuchida S, et al. Specific expression of glutathione Stransferase Pi forms in (pre)neoplastic tissues: their properties and functions [J]. Tohoku J Exp Med, 1992, 168(2): 97103.
16.	Hirai K, Sasahira T, Ohmori H, et al. Inhibition of heme oxygenase1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL mice [J]. Int J Cancer, 2007, 120(3): 500505.
17.	Tanaka S, Akaike T, Fang J, et al. Antiapoptotic effect of haem oxygenase1 induced by nitric oxide in experimental solid tumour [J]. Br J Cancer, 2003, 88(6): 902909.
18.	Yokoyama S, Mita S, Okabe A, et al. Prediction of radiosensitivity in human esophageal squamous cell carcinomas with heme oxygenase1: a clinicopathological and immunohistochemical study [J]. Oncol Rep, 2001, 8(2): 355358.

1. Motterlini R, Foresti R, Bassi R, et al. Endothelial heme oxygenase1 induction by hypoxia. Modulation by inducible nitricoxide synthase and Snitrosothiols [J]. J Biol Chem, 2000, 275(18): 1361313620.
2. Goodman AI, Choudhury M, da Silva JL, et al. Overexpression of the heme oxygenase gene in renal cell carcinoma [J]. Proc Soc Exp Biol Med, 1997, 214(1): 5461.
3. Maines MD, Abrahamsson PA.Expression of heme oxygenase1 (HSP32) in human prostate: normal, hyperplastic, and tumor tissue distribution [J]. Urology, 1996, 47(5): 727733.
4. Reiter TA, Demple B. Carbon monoxide mediates protection against nitric oxide toxicity in HeLa cells [J]. Free Radic Biol Med, 2005, 39(8): 10751088.
5. Wagener FA, da Silva JL, Farley T, et al. Differential effects of heme oxygenase isoforms on heme mediation of endothelial intracellular adhesion molecule 1 expression [J]. J Pharmacol Exp Ther， 1999， 291(1): 416423.
6. 张黎, 程力, 李更生, 等. 血红素氧化酶1在大鼠肝移植中保护作用的研究 [J]. 中国普外基础与临床杂志, 2008, 15(9): 665 670.
7. CordonCardo C, O’Brien JP, Boccia J, et al. Expression of the multidrug resistance gene product (Pglycoprotein) in human normal and tumor tissues [J]. J Histochem Cytochem, 1990, 38(9): 12771287.
8. 魏学明, 顾国利, 任力, 等. 多药耐药基因产物在胃癌组织中的表达及意义 [J]. 中国普外基础与临床杂志, 2009, 16(12): 10001004.
9. Berberat PO, Dambrauskas Z, Gulbinas A, et al. Inhibition of heme oxygenase1 increases responsiveness of pancreatic cancer cells to anticancer treatment [J]. Clin Cancer Res, 2005, 11(10): 37903798．.
10. 张隽开, 王忠裕, 丁大鹏，等. 血红素加氧酶对肝癌耐药细胞株Bel/Fu化疗敏感性的影响 [J]. 中华肿瘤防治杂志, 2009, 16(13): 990993．.
11. Yu DS, Lin JC, Hsieh DS, et al. Modulation of MDR1 gene by MIF and GSTpi with drug resistance generation in hormone independent prostate cancer [J]. Arch Androl, 2006, 52(4): 283291.
12. 薛军, 支学军, 屈明, 等. 胃癌及食管癌中肿瘤耐药标志物P糖蛋白和谷胱甘肽转移酶表达的研究 [J]. 中国普外基础与临床杂志, 2002, 9(5): F2.
13. Dirven HA, Dictus EL, Broeders NL, et al. The role of human glutathione Stransferase isoenzymes in the formation of glutathione conjugates of the alkylating cytostatic drug thiotepa [J]. Cancer Res, 1995, 55(8): 17011706.
14. Kuroda H, Sugimoto T, Ueda K, et al. Different drug sensitivity in two neuroblastoma cell lines established from the same patient before and after chemotherapy [J]. Int J Cancer, 1991, 47(5): 732737.
15. Sato K, Satoh K, Tsuchida S, et al. Specific expression of glutathione Stransferase Pi forms in (pre)neoplastic tissues: their properties and functions [J]. Tohoku J Exp Med, 1992, 168(2): 97103.
16. Hirai K, Sasahira T, Ohmori H, et al. Inhibition of heme oxygenase1 by zinc protoporphyrin IX reduces tumor growth of LL/2 lung cancer in C57BL mice [J]. Int J Cancer, 2007, 120(3): 500505.
17. Tanaka S, Akaike T, Fang J, et al. Antiapoptotic effect of haem oxygenase1 induced by nitric oxide in experimental solid tumour [J]. Br J Cancer, 2003, 88(6): 902909.
18. Yokoyama S, Mita S, Okabe A, et al. Prediction of radiosensitivity in human esophageal squamous cell carcinomas with heme oxygenase1: a clinicopathological and immunohistochemical study [J]. Oncol Rep, 2001, 8(2): 355358.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effect of ZnPP Ⅸ on HO-1 and GST-π Expressions and Chemosensitivity of Drug-Resistant Hepatic Carcinoma Cell Line Bel/Fu

Abstract Full text Figures/Tables Video References Cited by

Format

Content