Genistein Regulates bax Gene Expression and Induces Apoptosis in Hepatocellular Carcinoma HepG2 Cells_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

MA X ingbiao ¹ , Z HA N G J ihong ² , L IA N GL ij ian ³ , HUA N G J ief u ³

1. Department of Hepatobi l iary S urgery , The Fi rst A f f i l iated Hos pi tal of Guang dong Pharmaceutical Uni versi t y , Guangz hou 510080 , China;;
2. S urgical S taf f Room , Cl incical Col lege of Guang dong Pharmaceutical Uni versi t y , Guangz hou 510224 , China;;
3. Department of Hepatobi l iary S urgery , The Fi rst A f f i l iated Hos pi tal of SUN Yat2Sen Uni versi t y , Guangz hou 510080 , China;

Corresponding author：

Keywords：

Hepatocellular carcinoma,Genistein ,bax gene ,Cell apoptosis

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【 Abstract 】 Objective To probe into the role of inositol 1, 4, 5-trisphosphate (IP3) and bax gene expression in apoptosis of HepG2 cells induced by genistein (Gen). Methods HepG2 cells were treated with different concentrations including 20, 40, 60 and 80 μ mol/L Gen as HepG2 cells cultured with 0 μmol/L Gen for 72 h was control; HepG2 cells were treated with 60 μmol/L Gen for 6, 12, 24, 48 and 72 h as HepG2 cells treated with 60 μmol/L Gen for 0 h was control. IP3 content, bax mRNA expression and apoptosis rate were assayed by IP3- ［ 3H ］ Birtrak assay, RT-PCR and flow cytometry, respectively. ResultsHepG2 cells incubated with each concentration of Gen for 72 h ， IP3 content was lower than that of control 〔 (17.7 ± 1.3), (11.2 ± 0.9), (4.9 ± 0.5), (4.8 ± 0.3) pmol/106 cells vs (29.4 ± 0.5) pmol/106 cells 〕 , P ＜ 0.01 ； bax mRNA expression (RI which was the gray degree multiply area of bax/the gray degree multiply area of β -actin) was higher than that of control (0.26 ± 0.02, 0.33 ± 0.05, 0.35 ± 0.06, 0.38 ± 0.05 vs 0.09 ± 0.01), P ＜ 0.01 ； The apoptosis rate was higher than that of control 〔 (10.1 ± 0.9)%, (18.7 ± 1.6)%, 　 (28.7 ± 2.5)%, (27.9 ± 2.0)% vs (2.6 ± 0.1)% 〕 , P ＜ 0.01. HepG2 cells were incubated with 60 μ mol/L Gen for 6, 12, 24, 48 and 72 h ， IP3 content was lower than that of control 〔 (22.6 ± 0.9), (12.0 ± 1.4), (7.5 ± 0.8), (5.6 ± 0.5), (4.3 ± 0.6) pmol/106 cells vs (29.2 ± 0.6) pmol/106 cells 〕 , P ＜ 0.01 ； bax mRNA expression was higher than that of control incubated with 60 μ mol/L Gen for above 12 h (0.25 ± 0.06, 0.29 ± 0.02, 0.30 ± 0.02, 0.35 ± 0.04 vs 0.09 ± 0.01), P ＜ 0.01 ； The apoptosis rate in groups incubated with 60 μ mol/L Gen for 24, 48 and 72 h was significantly higher than that in control 〔 (7.4 ± 0.5)%, (20.5 ± 2.0)%, (30.7 ± 1.6)% vs (2.6 ± 0.1)% 〕 , P ＜ 0.01. ConclusionGen induces apoptosis of HepG2 cells by reducing IP3 production and increasing bax gene expression.

Citation： MA X ingbiao ,Z HA N G J ihong,L IA N GL ij ian,HUA N G J ief u. Genistein Regulates bax Gene Expression and Induces Apoptosis in Hepatocellular Carcinoma HepG2 Cells. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2008, 15(4): 245-249. doi: Copy

1.	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.
2.	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.
3.	Kountouras J, Zavos C, Chatzopoulos D. Apoptotic and anti-angiogenic strategies in liver and gastrointestinal malignancies [J]. J Surg Oncol, 2005; 90(4)∶249.
4.	Baskin-Bey ES, Gores GJ. Caspase-8, death-receptor signaling, and hepatocarcinogenesis: the Fas and the furious [J]. Gastroenterology, 2005; 129(5)∶1790.
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.
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.
7.	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.
8.	Csokay B, Prajda N, Weber G, et al. Molecular mechanisms in the antiproliferative action of quercetin [J]. Life Sci, 1997; 60(24)∶2157.
9.	Li Y, Sarkar FH. Gene expression profiles of genistein-treated PC3 prostate cancer cells [J]. J Nutr, 2002; 132(12)∶3623.
10.	Choi YH, Lee WH, Park KY, et al. p53-independent induction of p21WAF1/CIP1, reduction of cyclin B1 and G2/M arrest by the isoflavone genistein in human prostate carcinoma cells [J]. Jpn J Cancer Res, 2000; 91(2)∶164.
11.	Weber G, Shen F, Prajda N, et al. Regulation of the signal transduction program by drugs [J]. Adv Enzyme Regul, 1997; 37∶35.
12.	温静，万家椿. 信号转导治疗——疾病治疗的新途径 [J]. 医学综述，1997; 6（3）∶268.
13.	张继红, 梁力建, 黄洁夫. Genistein下调肝癌细胞survivin基因表达和诱导细胞凋亡的实验研究 [J]. 中国病理生理杂志，2006; 22（2）∶372.
14.	张继红, 梁力建, 黄洁夫, 等. Genistein 上调肝癌HepG2细胞PTEN基因表达诱导凋亡的实验研究 [J]. 中山大学学报（医学科学版），2006; 27（3）∶285.
15.	张继红, 梁力建, 黄洁夫, 等. Genistein调节肝癌细胞PTEN和survivin蛋白表达的实验研究 [J]. 中华普通外科杂志，2006; 21（9）∶654.
16.	Sanna MG, da Silva Correia J, Ducrey O, et al. IAP suppression of apoptosis involves distinct mechanisms: the TAK1/JNK1 signaling cascade and caspase inhibition [J]. Mol Cell Biol, 2002; 22(6)∶1754.
17.	徐宏勇，李开宗，付由池, 等. 人肝细胞癌中促凋亡基因bax的原位检测及其临床意义 [J]. 中国普外基础与临床杂志，2000; 7(4)∶238.
18.	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.
19.	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.
20.	连君，曹雪涛，于益芝. Bcl-2， bax与肿瘤细胞凋亡 [J]. 中国生物治疗杂志，2003; 10（3）∶232.
21.	Wiesenauer CA, Yip-Schneider MT, Wang Y, et al. Multiple anticancer effects of blocking MEK-ERK signaling in hepatocellular carcinoma [J]. J Am Coll Surg, 2004; 198(3)∶410.

1. 　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.
2. 　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.
3. 　Kountouras J, Zavos C, Chatzopoulos D. Apoptotic and anti-angiogenic strategies in liver and gastrointestinal malignancies [J]. J Surg Oncol, 2005; 90(4)∶249.
4. 　Baskin-Bey ES, Gores GJ. Caspase-8, death-receptor signaling, and hepatocarcinogenesis: the Fas and the furious [J]. Gastroenterology, 2005; 129(5)∶1790.
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.
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.
7. 　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.
8. 　Csokay B, Prajda N, Weber G, et al. Molecular mechanisms in the antiproliferative action of quercetin [J]. Life Sci, 1997; 60(24)∶2157.
9. 　Li Y, Sarkar FH. Gene expression profiles of genistein-treated PC3 prostate cancer cells [J]. J Nutr, 2002; 132(12)∶3623.
10. 　Choi YH, Lee WH, Park KY, et al. p53-independent induction of p21WAF1/CIP1, reduction of cyclin B1 and G2/M arrest by the isoflavone genistein in human prostate carcinoma cells [J]. Jpn J Cancer Res, 2000; 91(2)∶164.
11. 　Weber G, Shen F, Prajda N, et al. Regulation of the signal transduction program by drugs [J]. Adv Enzyme Regul, 1997; 37∶35.
12. 　温静，万家椿. 信号转导治疗——疾病治疗的新途径 [J]. 医学综述，1997; 6（3）∶268.
13. 　张继红, 梁力建, 黄洁夫. Genistein下调肝癌细胞survivin基因表达和诱导细胞凋亡的实验研究 [J]. 中国病理生理杂志，2006; 22（2）∶372.
14. 　张继红, 梁力建, 黄洁夫, 等. Genistein 上调肝癌HepG2细胞PTEN基因表达诱导凋亡的实验研究 [J]. 中山大学学报（医学科学版），2006; 27（3）∶285.
15. 　张继红, 梁力建, 黄洁夫, 等. Genistein调节肝癌细胞PTEN和survivin蛋白表达的实验研究 [J]. 中华普通外科杂志，2006; 21（9）∶654.
16. 　Sanna MG, da Silva Correia J, Ducrey O, et al. IAP suppression of apoptosis involves distinct mechanisms: the TAK1/JNK1 signaling cascade and caspase inhibition [J]. Mol Cell Biol, 2002; 22(6)∶1754.
17. 　徐宏勇，李开宗，付由池, 等. 人肝细胞癌中促凋亡基因bax的原位检测及其临床意义 [J]. 中国普外基础与临床杂志，2000; 7(4)∶238.
18. 　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.
19. 　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.
20. 　连君，曹雪涛，于益芝. Bcl-2， bax与肿瘤细胞凋亡 [J]. 中国生物治疗杂志，2003; 10（3）∶232.
21. 　Wiesenauer CA, Yip-Schneider MT, Wang Y, et al. Multiple anticancer effects of blocking MEK-ERK signaling in hepatocellular carcinoma [J]. J Am Coll Surg, 2004; 198(3)∶410.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Genistein Regulates bax Gene Expression and Induces Apoptosis in Hepatocellular Carcinoma HepG2 Cells

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