• 1.中山大學(xué)附屬第一醫(yī)院黃埔院區(qū)肝膽外科（廣州 510070）;;
  • 2.中山大學(xué)附屬第一醫(yī)院肝膽外科（廣州 510080）;

目的  探討三磷酸肌醇(IP3)和bcl-2基因表達(dá)變化在槲皮素治療裸鼠移植人肝細(xì)胞癌中的作用。方法  建立裸鼠移植人肝細(xì)胞癌模型，對(duì)照組腹腔注入含0.4% DMSO的RPMI 1640培養(yǎng)基0.05 ml/（g·d），槲皮素治療組腹腔注入槲皮素 50 mg/(kg·d)，3周后觀察肝癌生長(zhǎng)情況，并應(yīng)用IP3-［3H］ Birtrak Assay試劑盒檢測(cè)肝癌組織中IP3的含量,RT-PCR檢測(cè)肝癌組織中bcl-2 mRNA的表達(dá)，Western blot檢測(cè)肝癌組織中bcl-2蛋白的表達(dá)。結(jié)果  槲皮素治療組移植瘤體積和重量均明顯小于或輕于對(duì)照組〔體積: （15.8±10.1） mm3比（52.3±26.5） mm3，重量: （44.8±10.4） mg比（91.3±31.4） mg，P＜0.01〕； 肝癌組織中IP3含量明顯低于對(duì)照組〔（13.4±1.4） pmol/mg prot比（35.3±6.6） pmol/mg prot，P＜0.01〕，bcl-2 mRNA表達(dá)低于對(duì)照組但差異無(wú)統(tǒng)計(jì)學(xué)意義〔RI（相對(duì)灰度與面積之積）: 0.55±0.05比0.79±0.19，P＞0.05〕，bcl-2蛋白的表達(dá)則明顯低于對(duì)照組〔RI: 1.07±0.12比6.69±1.80，P＜0.01〕。結(jié)論  槲皮素能減少IP3的生成,下調(diào)肝癌組織中bcl-2基因的表達(dá),抑制裸鼠移植人肝細(xì)胞癌的生長(zhǎng)。

引用本文： 張繼紅,梁力建,黃潔夫. bcl-2基因表達(dá)變化在槲皮素抑制肝細(xì)胞癌生長(zhǎng)中的作用. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009, 16(6): 455-459. doi: 復(fù)制

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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.
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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. 楊連君， 曹雪濤， 于益芝. bcl-2, bax與腫瘤細(xì)胞凋亡 [Ｊ]. 中國(guó)腫瘤生物治療雜志， 2003; 10（3）： 232-234.
12. Nicholson DW, Thornberry NA. Apoptosis. Life and death decisions [Ｊ]. Science, 2003; 299(5604): 214-215.
13. 劉戰(zhàn)培， 嚴(yán)律南. bcl-2蛋白在肝細(xì)胞肝癌發(fā)生過程中的表達(dá)及其與肝細(xì)胞凋亡變化的關(guān)系 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志, 1999; 6(4)： 193-195.
14. 于冰， 孫治君. 凋亡相關(guān)基因bcl-2、 bax、 bad與乳腺癌 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2007; 14(6): 739-742.
15. 陳華， 景在平， 包俊敏， 等. RNA干擾對(duì)兔血管平滑肌細(xì)胞bcl-2基因表達(dá)的影響 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志, 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. 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. 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. 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. 4. 孫大業(yè)， 郭艷林， 馬力耕主編. 細(xì)胞信號(hào)轉(zhuǎn)導(dǎo) [M]. 第2版. 北京： 科學(xué)出版社, 2000: 1-9.
  5. 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. 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. 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. 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. 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. 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. 11. 楊連君， 曹雪濤， 于益芝. bcl-2, bax與腫瘤細(xì)胞凋亡 [Ｊ]. 中國(guó)腫瘤生物治療雜志， 2003; 10（3）： 232-234.
  12. 12. Nicholson DW, Thornberry NA. Apoptosis. Life and death decisions [Ｊ]. Science, 2003; 299(5604): 214-215.
  13. 13. 劉戰(zhàn)培， 嚴(yán)律南. bcl-2蛋白在肝細(xì)胞肝癌發(fā)生過程中的表達(dá)及其與肝細(xì)胞凋亡變化的關(guān)系 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志, 1999; 6(4)： 193-195.
  14. 14. 于冰， 孫治君. 凋亡相關(guān)基因bcl-2、 bax、 bad與乳腺癌 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2007; 14(6): 739-742.
  15. 15. 陳華， 景在平， 包俊敏， 等. RNA干擾對(duì)兔血管平滑肌細(xì)胞bcl-2基因表達(dá)的影響 [Ｊ]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2007; 14（1）： 56-58.
  16. 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. 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. 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. 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. 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.