Role of bcl-2 Gene Expression in Inhibiting The Growth of Hepatocellular Carcinoma of Nude Mice by Quercetin_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Jihong ¹ , LIANG Lijian ² , HUANG Jiefu ²

1.Division of Hepato-Biliary Surgery, The Huangpu Hospital,The First Affiliated Hospital of SUN Yat-sen University, Guangzhou 510070, China;;
2.Division of Hepato-Biliary Surgery, The First Affiliated Hospital of SUN Yat-sen University, Guangzhou 510080, China;

Corresponding author：

Keywords：

Hepatocellular carcinoma; Quercetin; bcl-2 gene; Inositol triphosphate; Signal transduction

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Objective To probe into the roles of inositol 1, 4, 5-trisphosphate (IP3) and bcl-2 gene expression in inhabiting hepatocellular carcinoma of nude mice by quercetin. Methods Animals with hepatocellular carcinoma in quercetin group were treated with injection peritoneum of quercetin 50 mg/（kg·d ） for 3 weeks, while which in control group were treated with 0.4% DMSO of RPMI 1640 0.05 ml/（g·d）. Then the volume and the weight of tumors were measured, IP3, bcl-2 mRNA and bcl-2 protein were assayed by IP3-［3H］ Birtrak Assay, RT-PCR and Western blot respectively. Results The volume and weight of tumors in quercetin group were lower than those in control group 〔（15.8±10.1） mm3 vs. （52.3±26.5） mm3 in volume, （44.8±10.4） mg vs.（91.3±31.4） mg in weight， P＜0.01〕. Content of IP3 in quercetin group was lower than that in control group 〔（13.4±1.4） pmol/mg prot vs. （35.3±6.6） pmol/mg prot， P＜0.01〕. There was no significant difference in bcl-2 mRNA expression between quercetin group and control group 〔RI （the gray degree multiply area of bcl-2 /the gray degree multiply area of β-actin）： 0.55±0.05 vs. 0.79±0.19， P＞0.05〕， but the expression of bcl-2 protein in quercetin group was lower than that in control group (RI: 1.07±0.12 vs. 6.69±1.80, P＜0.01). Conclusion Quercetin can inhabit the growth of hepatocellular carcinoma tansplanted into liver of nude mice by reducing IP3 production and down-regulating bcl-2 gene expression.

Citation： ZHANG Jihong,LIANG Lijian,HUANG Jiefu. Role of bcl-2 Gene Expression in Inhibiting The Growth of Hepatocellular Carcinoma of Nude Mice by Quercetin. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2009, 16(6): 455-459. doi: Copy

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12.	Nicholson DW, Thornberry NA. Apoptosis. Life and death decisions [Ｊ]. Science, 2003; 299(5604): 214-215.
13.	刘战培，严律南. bcl-2蛋白在肝细胞肝癌发生过程中的表达及其与肝细胞凋亡变化的关系 [Ｊ]. 中国普外基础与临床杂志, 1999; 6(4)： 193-195.
14.	于冰，孙治君. 凋亡相关基因bcl-2、 bax、 bad与乳腺癌 [Ｊ]. 中国普外基础与临床杂志, 2007; 14(6): 739-742.
15.	陈华，景在平，包俊敏，等. RNA干扰对兔血管平滑肌细胞bcl-2基因表达的影响 [Ｊ]. 中国普外基础与临床杂志, 2007; 14（1）： 56-58.
16.	Mozhayeva GN, Naumov AP, Kuryshev YA. Inositol 1,4,5-trisphosphate activates two types of Ca2+-permeable channels in human carcinoma cells [Ｊ]. FEBS Lett, 1990; 277(1-2): 233-234.
17.	Feldner JC, Brandt BH. Cancer cell motility-on the road from c-erbB-2 receptor steered signaling to actin reorganization [Ｊ]. Exp Cell Res, 2002; 272(2): 93-108.
18.	Rodland KD, Wersto RP, Hobson S, et al. Thapsigargin-induced gene expression in nonexcitable cells is dependent on calcium influx [Ｊ]. Mol Endocrinol, 1997; 11(3): 281-291.
19.	Schulte-Hermann R, Bursch W, Lw-Baselli A, et al. Apoptosis in the liver and its role in hepatocarcinogenesis [Ｊ]. Cell Biol Toxicol, 1997; 13(4-5): 339-348.
20.	Grasl-Kraupp B, Ruttkay-Nedecky B, Müllauer L, et al. Inherent increase of apoptosis in liver tumors: implications for carcinogenesis and tumor regression [Ｊ]. Hepatology, 1997; 25(4): 906-912.

1. ] Duan XX, Ou JS, Li Y,　 et al. Dynamic expression of apoptosis-related genes during development of laboratory hepatocellular carcinoma and its relation to apoptosis [Ｊ]. World J Gastroenterol， 2005;　11(30): 4740-4744.
2. Kountouras J, Zavos C, Chatzopoulos D. Apoptotic and anti-angiogenic strategies in liver and gastrointestinal malignancies [Ｊ]. J Surg Oncol, 2005; 90(4): 249-259.
3. Baskin-Bey ES, Gores GJ. Caspase-8, death-receptor signaling, and hepatocarcinogenesis: the Fas and the furious [Ｊ]. Gastroenterology, 2005; 129(5): 1790-1792.
4. 孙大业，郭艳林，马力耕主编. 细胞信号转导 [M]. 第2版. 北京：科学出版社, 2000: 1-9.
5. Singhal RL, Yeh YA, Look KY, et al. Coordinated increase in activities of the signal transduction enzymes PI kinase and PIP kinase in human cancer cells [Ｊ]. Life Sci, 1994; 55(19): 1487-1492.
6. Shen F, Xue X, Weber G. Tamoxifen and genistein synergistically down-regulate signal transduction and proliferation in estrogen receptor-negative human breast carcinoma MDA-MB-435 cells [Ｊ]. Anticancer Res, 1999; 19(3A): 1657-1662.
7. Weber G, Shen F, Prajda N, et al. Increased signal transduction activity and down-regulation in human cancer cells [Ｊ]. Anticancer Res, 1996; 16(6A): 3271-3282.
8. Csokay B, Prajda N, Weber G, et al. Molecular mechanisms in the antiproliferative action of quercetin [Ｊ]. Life Sci, 1997; 60(24): 2157-2163.
9. Weber G, Shen F, Prajda N, et al. Regulation of the signal transduction program by drugs [Ｊ]. Adv Enzyme Regul, 1997; 37: 35-55.
10. Yang E, Zha J, Jockel J, et al. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death [Ｊ]. Cell, 1995; 80(2): 285-291.
11. 杨连君，曹雪涛，于益芝. bcl-2, bax与肿瘤细胞凋亡 [Ｊ]. 中国肿瘤生物治疗杂志， 2003; 10（3）： 232-234.
12. Nicholson DW, Thornberry NA. Apoptosis. Life and death decisions [Ｊ]. Science, 2003; 299(5604): 214-215.
13. 刘战培，严律南. bcl-2蛋白在肝细胞肝癌发生过程中的表达及其与肝细胞凋亡变化的关系 [Ｊ]. 中国普外基础与临床杂志, 1999; 6(4)： 193-195.
14. 于冰，孙治君. 凋亡相关基因bcl-2、 bax、 bad与乳腺癌 [Ｊ]. 中国普外基础与临床杂志, 2007; 14(6): 739-742.
15. 陈华，景在平，包俊敏，等. RNA干扰对兔血管平滑肌细胞bcl-2基因表达的影响 [Ｊ]. 中国普外基础与临床杂志, 2007; 14（1）： 56-58.
16. Mozhayeva GN, Naumov AP, Kuryshev YA. Inositol 1,4,5-trisphosphate activates two types of Ca2+-permeable channels in human carcinoma cells [Ｊ]. FEBS Lett, 1990; 277(1-2): 233-234.
17. Feldner JC, Brandt BH. Cancer cell motility-on the road from c-erbB-2 receptor steered signaling to actin reorganization [Ｊ]. Exp Cell Res, 2002; 272(2): 93-108.
18. Rodland KD, Wersto RP, Hobson S, et al. Thapsigargin-induced gene expression in nonexcitable cells is dependent on calcium influx [Ｊ]. Mol Endocrinol, 1997; 11(3): 281-291.
19. Schulte-Hermann R, Bursch W, Lw-Baselli A, et al. Apoptosis in the liver and its role in hepatocarcinogenesis [Ｊ]. Cell Biol Toxicol, 1997; 13(4-5): 339-348.
20. Grasl-Kraupp B, Ruttkay-Nedecky B, Müllauer L, et al. Inherent increase of apoptosis in liver tumors: implications for carcinogenesis and tumor regression [Ｊ]. Hepatology, 1997; 25(4): 906-912.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Role of bcl-2 Gene Expression in Inhibiting The Growth of Hepatocellular Carcinoma of Nude Mice by Quercetin

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