目的 探討槲皮素對人乳腺癌細(xì)胞的作用及其相關(guān)機(jī)理。
方法 分別以 12.5、25、50、100及200 μmol/L終濃度的槲皮素作用于人乳腺癌細(xì)胞MDA-MB-435S,運(yùn)用臺盼藍(lán)拒染法檢測槲皮素對乳腺癌細(xì)胞的細(xì)胞抑制率,流式細(xì)胞術(shù)分析槲皮素對乳腺癌細(xì)胞增殖周期的影響,RT-PCR 法檢測乳腺癌細(xì)胞中細(xì)胞凋亡蛋白酶3(caspase-3) mRNA表達(dá)水平。
結(jié)果 槲皮素能抑制人乳腺癌細(xì)胞的增殖,且與藥物的劑量及作用時間有關(guān);槲皮素能改變?nèi)橄侔┘?xì)胞周期的分布,隨著槲皮素濃度的增加,G0/G1 期細(xì)胞所占比例減少,S 期細(xì)胞所占比例增加,G2/M 期細(xì)胞比例先增加后減少; 槲皮素能夠激活乳腺癌細(xì)胞中caspase-3的表達(dá)。
結(jié)論 槲皮素能夠抑制人乳腺癌細(xì)胞的增殖并誘導(dǎo)其凋亡,其機(jī)理可能是通過改變細(xì)胞周期的分布及上調(diào)caspase-3的表達(dá)實現(xiàn)的。
引用本文: 李世正,李昆,張俊華,李錦成,單吉賢. 槲皮素在人乳腺癌細(xì)胞中抑制增殖和誘導(dǎo)凋亡的作用. 中國普外基礎(chǔ)與臨床雜志, 2009, 16(2): 124-128. doi: 復(fù)制
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2. | IWase Y, Takemura Y, Ju-ichi M, et al. Inhibitory effect of flavonoid derivatives on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors [J]. Cancer Lett, 2001; 173(2): 105. |
3. | Kim WK, Bang MH, Kim ES, et al. Quercetin decreases the expression of ErbB2 and ErbB3 proteins in HT-29 human colon cancer cells [J]. J Nutr Biochem, 2005; 16(3): 155. |
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6. | 柯尊金, 丁心喜, 董文奎, 等.槲皮素對人膀胱癌BIU-87細(xì)胞增殖和凋亡的影響[J].實用癌癥雜志, 2008; 23(2): 116. |
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10. | 王玉, 孫黎光, 夏春輝.Caspase介導(dǎo)的Fas凋亡途徑 [J].世界華人消化雜志, 2006; 14(36): 3439. |
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12. | 馬銀斌, 吳誠義, 陳鑫.As2O3對人乳腺癌中NF-κB p65、survivin和caspase-3的作用及相關(guān)性研究[J].中國普外基礎(chǔ)與臨床雜志, 2006; 13(4):409. |
13. | 聞春生, 應(yīng)斌武, 張永剛, 等. 槲皮素對肺腺癌細(xì)胞株A549細(xì)胞中凋亡相關(guān)因子caspase-3表達(dá)的影響[J].中國肺癌雜志, 2008; 11(2):194. |
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21. | Lim HA, Kim JH, Kim JH, et al. Genistein induces glucose-regulated protein 78 in mammary tumor cell [J]. J Med Food, 2006; 9(1): 28. |
22. | Akbas SH, Timur M, Ozben T. The effect of quercetin on topotecan cytotoxicity in MCF-7 and MDA-MB 231 human breast cancer cells [J]. J Surg Res, 2005; 125(1):49. |
- 1. Hollman PC, Katan MB. Dietary flavonoids: intake, health effects and bioavailability [J]. Food Chem Toxicol, 1999; 37(9-10): 937.
- 2. IWase Y, Takemura Y, Ju-ichi M, et al. Inhibitory effect of flavonoid derivatives on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors [J]. Cancer Lett, 2001; 173(2): 105.
- 3. Kim WK, Bang MH, Kim ES, et al. Quercetin decreases the expression of ErbB2 and ErbB3 proteins in HT-29 human colon cancer cells [J]. J Nutr Biochem, 2005; 16(3): 155.
- 4. Yang JH, Hsia TC, Kuo HM, et al. Inhibition of lung cancer cell growth by quercetin glucuronides via G2/M arrest and induction of apoptosis[J]. Drug Metab Dispos, 2006; 34(2): 296.
- 5. 沈麗霞, 徐惠玉, 趙丕文, 等.槲皮素對人類乳腺癌細(xì)胞增殖的影響[J]. 中國中醫(yī)藥信息雜志, 2008; 15(3): 30.
- 6. 柯尊金, 丁心喜, 董文奎, 等.槲皮素對人膀胱癌BIU-87細(xì)胞增殖和凋亡的影響[J].實用癌癥雜志, 2008; 23(2): 116.
- 7. Hartwell LH, Kastan MB. Cell cycle control and cancer [J]. Science, 1994; 266(5192): 1821.
- 8. Hartwell LH, Weinert TA. Checkpoints: controls that ensure the order of cell cycle events [J]. Science, 1989; 246(4930): 629.
- 9. Chiarugi V, Magnelli L, Cinelli M, et al. Apoptosis and the cell cycle [J]. Cell Mol Biol Res, 1994; 40(7-8): 603.
- 10. 王玉, 孫黎光, 夏春輝.Caspase介導(dǎo)的Fas凋亡途徑 [J].世界華人消化雜志, 2006; 14(36): 3439.
- 11. 金琳芳,陳同鈺.Bcl-2基因蛋白家族與細(xì)胞凋亡[J].醫(yī)學(xué)綜述, 2005; 11(5): 446.
- 12. 馬銀斌, 吳誠義, 陳鑫.As2O3對人乳腺癌中NF-κB p65、survivin和caspase-3的作用及相關(guān)性研究[J].中國普外基礎(chǔ)與臨床雜志, 2006; 13(4):409.
- 13. 聞春生, 應(yīng)斌武, 張永剛, 等. 槲皮素對肺腺癌細(xì)胞株A549細(xì)胞中凋亡相關(guān)因子caspase-3表達(dá)的影響[J].中國肺癌雜志, 2008; 11(2):194.
- 14. van der Woude H, Gliszczyńska-Swigo A, Struijs K, et al. Biphasic modulation of cell proliferation by quercetin at concentrations physiologically relevant in humans [J]. Cancer Lett, 2003; 200(1): 41.
- 15. Sarkar FH, Li Y. Mechanisms of cancer chemoprevention by soy isoflavone genistein [J]. Cancer Metastasis Rev, 2002; 21 (3-4): 265.
- 16. Li Z, Li J, Mo B, et al. Genistein induces G2/M cell cycle arrest via stable activation of ERK1/2 pathway in MDA-MB-231 breast cancer cells [J]. Cell Biol Toxicol, 2008; 24(5): 401.
- 17. Conklin CM, Bechberger JF, MacFabe D, et al. Genistein and quercetin increase connexin43 and suppress growth of breast cancer cells [J]. Carcinogenesis, 2007; 28(1): 93.
- 18. Shao ZM, Shen ZZ, Fontana JA, et al. Genistein’s “ER-dependent and independent” actions are mediated through ER pathways in ER-positive breast carcinoma cell lines [J]. Anticancer Res, 2000; 20(4):2409.
- 19. Vissac-Sabatier C, Bignon YJ, Bernard-Gallon DJ. Effects of the phytoestrogens genistein and daidzein on BRCA2 tumor suppressor gene expression in breast cell lines [J]. Nutr Cancer, 2003; 45(2): 247.
- 20. Kousidou OC, Mitropoulou TN, Roussidis AE, et al. Genistein suppresses the invasive potential of human breast cancer cells through transcriptional regulation of metalloproteinases and their tissue inhibitors [J]. Int J Oncol, 2005; 26(4): 1101.
- 21. Lim HA, Kim JH, Kim JH, et al. Genistein induces glucose-regulated protein 78 in mammary tumor cell [J]. J Med Food, 2006; 9(1): 28.
- 22. Akbas SH, Timur M, Ozben T. The effect of quercetin on topotecan cytotoxicity in MCF-7 and MDA-MB 231 human breast cancer cells [J]. J Surg Res, 2005; 125(1):49.