莪术醇对乳腺癌细胞MDA-MB-231侵袭能力的影响
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摘要
目的探讨莪术醇对乳腺癌MDA-MB-231细胞增殖能力、侵袭能力的影响。方法利用MTT实验检测乳腺癌MDA-MB-231细胞的增殖能力;应用基质胶侵袭小室实验检测乳腺癌MDA-MB-231细胞的侵袭能力;采用real-time PCR法检测经不同浓度的莪术醇药物干预的MDA-MB-231细胞,观察羟基末端结合蛋白1(CtBP1)在不同组中表达的变化。结果不同浓度的莪术醇(100、50、25、12.5μg/mL)处理下,细胞数量呈差异性、阶梯状下降,浓度为100μg/mL的细胞数量减少最为明显,差异有统计学意义(P<0.05)。同时细胞侵袭能力按药物浓度递减而减弱,差异有统计学意义(P<0.05)。Real-time PCR的结果显示,莪术醇可显著下调MDA-MB-231中CtBP1的表达(P=0.000)。结论莪术醇对乳腺癌MDA-MB-231细胞增殖有明显的抑制作用,对其侵袭能力亦有较强影响,药物浓度越高抑制增殖、侵袭、下调CtBP1表达的效果越明显。
Objective To evaluate the effects of curcumol on multiplication and invasiveness capacities of breast cancer cell MDA-MB-231.Methods The multiplication and invasiveness capacities of MDA-MB-231 cells were assessed with MTT assay and transwell test,respectively;while the expression of CtBP1 in different concentrations of curcumol was evaluated with real-time PCR.Results Significant inhibition on the multiplication and invasiveness capacities of MDA-MB-231 cells were revealed by curcumol on concentration-dependent manner(P < 0.05).Meanwhile,significant down-regulation of CtBP1 was observed by curcumol in MDA-MB-231 cells(P = 0.000).Conclusion Curcumol can inhibit the proliferation of MDA-MB-231 cells,induce apoptosis,impact the invasive ability,and down regulate the expression of CtBP1 in concentration-dependent manners.
Objective To evaluate the effects of curcumol on multiplication and invasiveness capacities of breast cancer cell MDA-MB-231.Methods The multiplication and invasiveness capacities of MDA-MB-231 cells were assessed with MTT assay and transwell test,respectively;while the expression of CtBP1 in different concentrations of curcumol was evaluated with real-time PCR.Results Significant inhibition on the multiplication and invasiveness capacities of MDA-MB-231 cells were revealed by curcumol on concentration-dependent manner(P < 0.05).Meanwhile,significant down-regulation of CtBP1 was observed by curcumol in MDA-MB-231 cells(P = 0.000).Conclusion Curcumol can inhibit the proliferation of MDA-MB-231 cells,induce apoptosis,impact the invasive ability,and down regulate the expression of CtBP1 in concentration-dependent manners.
引文
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[20]KUPPUSWAMY M,VIJAYALINGAM S,ZHAO L J,et al.Roleof the PLDLS-binding cleft region of CtBP1 in recruitment of coreand auxiliary components of the corepressor complex[J].Mol CellBiol,2008,28(1):269-281.
[21]FANG M,LI J,BLAUWKAMP T,et al.C-terminal-bindingprotein directly activates and represses Wnt transcriptional targetsin Drosophila[J].EMBO J,2006,25(12):2735-2745.
[22]WEI J,KATHLEEN W S,WILLIAM N,et al.Involvement of Ct-BP1 in the transcriptional activation of the MDR1 gene in humanmultidrug resistant cancer cells[J].Biochem Pharmacol,2007,74(6):851-859.
[23]CHINNADURAI G.The transcriptional corepressor CtBP:a foe ofmultiple tumor suppressors[J].Cancer Res,2009,69(3):731-734.
[24]ZHANG Q,WANG S Y,NOTTKE A C,et al.Redox sensor CtBPmediates hypoxia-induced tumor cell migration[J].Proc NatlAcad Sci U S A,2006,103(24):9029-9033.
[25]PENA C,GARCIA J M,GARCIA V,et al.The expression levelsof the transcriptional regulators p300 and CtBP modulate the corre-lations between SNAIL,ZEB1,E-cadherin and vitamin D recep-tor in human colon carcinomas[J].Int J Cancer,2006,119(9):2098-2104.
[26]POSTIGO A A,DEPP J L,TAYLOR J J,et al.Regulation ofSmad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins[J].EMBO J,2003,22(10):2453-2462.
[27]黄承信,曾思恩,肖胜军,等.CtBP与肿瘤相关的研究[J].当代医学,2011,35(23):38-41.
[2]钟章峰,陈修平,吴铁,等.莪术醇的研究进展[J].中国药房,2010,21(31):2959-2961.
[3]徐立春,边可君,刘志敏,等.天然药物莪术醇抑制肿瘤细胞生长及RNA合成影响的研究[J].肿瘤,2005,25(6):570-572.
[4]徐立春,边可君,卜平,等.莪术醇修饰的肿瘤疫苗抗MFC效应的研究[J].现代肿瘤医学,2006,14(11):1357-1359.
[5]徐立春,陈平,孙振华,等.莪术醇瘤苗治疗胃癌的实验研究[J].现代肿瘤医学,2008,16(12):2066-2069.
[6]MAUGHAN K L,LUTTERBIE M A,HAM P S.Treatment ofbreast cancer[J].Am Fam Physician,2010,81(11):1339-1346.
[7]张士勇.中药活性成分对乳腺癌细胞干预的研究进展[J].安徽医药,2009,13(12):1456-1458.
[8]曾建红,黄庆龙,陈旭,等.莪术抗癌活性成分的研究进展[J].中华中医药杂志,2008,23(5):1673-1727.
[9]肖胜军,张小玲,容明智,等.转录抑制因子CtBP1与其靶基因E-cadherin在结肠癌中的表达[J].世界华人消化杂志,2009,17(36):3756-3759.
[10]宋爱莉,殷玉琨.莪术油干预治疗肿瘤的研究及应用概况[J].山东中医药大学学报,2008,32(2):172-174.
[11]盛辉,苑春莉,王医术.莪术油对肺癌SPC2A4细胞株的体外抑制作用[J].江西中医学院学报,2006,18(5):51-52.
[12]唐渊,李晓辉.莪术提取物对肝癌细胞系HepG2的抗癌作用及机制研究[J].中国药理学通报,2007,23(6):790-794.
[13]王娟,王顺启,倪虹,等.莪术挥发油抑制人肝癌细胞株SMMC-7721生长的实验研究[J].天津中医药,2003,20(1):48-51.
[14]吴万垠,郭伟剑,常钢.莪术油微球释放莪术油对人肝癌SMMC27721细胞的作用[J].世界华人消化杂志,2003,11(3):260-263.
[15]吴万垠,邓嵘,区勇全.经肝动脉灌注莪术油微球对大鼠移植性肝癌的治疗作用[J].中华肝脏病杂志,2000,8(1):24-26.
[16]湛学军,徐燕萍,谢大泽,等.发光法分析莪术油等中药对肝、胃癌细胞增殖活性抑制作用的实验研究[J].中国肿瘤临床,2007,34(1):30-31.
[17]PAYANKAULAM S,LI L M,ARNOSTI D N.Transcriptional re-pressio n:conserved and evolved features[J].Curr Biol,2010,20(17):764-771.
[18]CORDA D,COLANZI A,LUINI A.The multiple activities of Ct-BP/BARS proteins:the golgi view[J].Trends Cell Biol,2006,16(3):167-173.
[19]CARCEDO C H,BONAZZI M,TURACCHIO G,et al.GolgiFragmentation during mitosis requires the membrane fissioning pro-tein CtBP3/BARS[J].Science,2004,305(5680):93-96.
[20]KUPPUSWAMY M,VIJAYALINGAM S,ZHAO L J,et al.Roleof the PLDLS-binding cleft region of CtBP1 in recruitment of coreand auxiliary components of the corepressor complex[J].Mol CellBiol,2008,28(1):269-281.
[21]FANG M,LI J,BLAUWKAMP T,et al.C-terminal-bindingprotein directly activates and represses Wnt transcriptional targetsin Drosophila[J].EMBO J,2006,25(12):2735-2745.
[22]WEI J,KATHLEEN W S,WILLIAM N,et al.Involvement of Ct-BP1 in the transcriptional activation of the MDR1 gene in humanmultidrug resistant cancer cells[J].Biochem Pharmacol,2007,74(6):851-859.
[23]CHINNADURAI G.The transcriptional corepressor CtBP:a foe ofmultiple tumor suppressors[J].Cancer Res,2009,69(3):731-734.
[24]ZHANG Q,WANG S Y,NOTTKE A C,et al.Redox sensor CtBPmediates hypoxia-induced tumor cell migration[J].Proc NatlAcad Sci U S A,2006,103(24):9029-9033.
[25]PENA C,GARCIA J M,GARCIA V,et al.The expression levelsof the transcriptional regulators p300 and CtBP modulate the corre-lations between SNAIL,ZEB1,E-cadherin and vitamin D recep-tor in human colon carcinomas[J].Int J Cancer,2006,119(9):2098-2104.
[26]POSTIGO A A,DEPP J L,TAYLOR J J,et al.Regulation ofSmad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins[J].EMBO J,2003,22(10):2453-2462.
[27]黄承信,曾思恩,肖胜军,等.CtBP与肿瘤相关的研究[J].当代医学,2011,35(23):38-41.