姜黄素抑制宫颈癌Hela细胞增殖机制研究
摘要
目的:研究姜黄素对宫颈癌Hela细胞P53基因以及乙酰化组蛋H3表达的影响,探讨其抑制Hela细胞增殖的机制。
方法:用不同浓度(0, 50,25,12.5,6.25,3.125μmol/L)的姜黄素作用于Hela细胞,在作用的不同时间(0,24,48,72h),用MTT法测定姜黄素对Hela细胞抑制增殖的效应;Rt-PCR法检测P53 mRNA的表达;Western blot法检测乙酰化组蛋白H3、乙酰化P53以及P53蛋白的表达。
结果:姜黄素以时间和剂量依赖方式抑制Hela细胞增殖;能明显上调组蛋白H3的乙酰化水平,促进P53的乙酰化和P53基因mRNA和相应蛋白的表达。
结论:姜黄素抑制宫颈癌Hela细胞增殖是通过上调组蛋白H3乙酰化水平,促进肿瘤抑制因子P53的活化与表达进行的。姜黄素具有去乙酰化酶抑制剂作用,有望开发用于治疗宫颈癌。
Objective To investigate the effects of curcumin on the acetylation of histone H3, P53 gene and the proliferation of cervical cancer cell line Hela.
Methods Hela cells were treated with different concentrations of curcumin(0, 50, 25, 12.5, 6.25, 3.125μmol/L) for different time(0,24,48,72h), MTT assay was performed to examin the growth inhibition effects of curcumin on Hela cells. The expression of P53 was assayed by reverse transcriptase polymerase chain reaction(Rt-PCR). The expressions of acetylated histone H3, P53 and acetylated P53 protein were determined by western blot.
Results Curcumin could inhibit the proliferation of Hela cells in a time-and- dose- dependent manner. The expression of P53 mRNA was different with the concentration and time of curcumin, which was the strongest in 25μmol/L at 48h. The levels of histone H3 acetylation, P53 expression and P53 acetylation were increased significantly when treated with different concentrations of curcumin for different time.
Conclusion Curcumin functions as a deacetylase inhibitor, which could increase the level of acetylated histone H3, enhance the expression and activity of tumor suppressor P53 and inhibit the proliferation of cervical cancer cell line Hela.
方法:用不同浓度(0, 50,25,12.5,6.25,3.125μmol/L)的姜黄素作用于Hela细胞,在作用的不同时间(0,24,48,72h),用MTT法测定姜黄素对Hela细胞抑制增殖的效应;Rt-PCR法检测P53 mRNA的表达;Western blot法检测乙酰化组蛋白H3、乙酰化P53以及P53蛋白的表达。
结果:姜黄素以时间和剂量依赖方式抑制Hela细胞增殖;能明显上调组蛋白H3的乙酰化水平,促进P53的乙酰化和P53基因mRNA和相应蛋白的表达。
结论:姜黄素抑制宫颈癌Hela细胞增殖是通过上调组蛋白H3乙酰化水平,促进肿瘤抑制因子P53的活化与表达进行的。姜黄素具有去乙酰化酶抑制剂作用,有望开发用于治疗宫颈癌。
Objective To investigate the effects of curcumin on the acetylation of histone H3, P53 gene and the proliferation of cervical cancer cell line Hela.
Methods Hela cells were treated with different concentrations of curcumin(0, 50, 25, 12.5, 6.25, 3.125μmol/L) for different time(0,24,48,72h), MTT assay was performed to examin the growth inhibition effects of curcumin on Hela cells. The expression of P53 was assayed by reverse transcriptase polymerase chain reaction(Rt-PCR). The expressions of acetylated histone H3, P53 and acetylated P53 protein were determined by western blot.
Results Curcumin could inhibit the proliferation of Hela cells in a time-and- dose- dependent manner. The expression of P53 mRNA was different with the concentration and time of curcumin, which was the strongest in 25μmol/L at 48h. The levels of histone H3 acetylation, P53 expression and P53 acetylation were increased significantly when treated with different concentrations of curcumin for different time.
Conclusion Curcumin functions as a deacetylase inhibitor, which could increase the level of acetylated histone H3, enhance the expression and activity of tumor suppressor P53 and inhibit the proliferation of cervical cancer cell line Hela.
引文
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8.吴孝杰,庞江琳,孙显斌,姜黄素及其联合化疗对子宫颈癌Hela细胞体外增殖的影响.华夏医学,2005,18(4):534-536.
9.王菁鹏,林青,姜黄素对子宫颈癌HeLa细胞的抑制作用.现代医药卫生,2006,22(16):2435-2437.
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3. Inaro H ,Onada M , Inafuku N ,Kubota M , Kamada Y, Osawa T , Kobayashi H , Wakabayashi K . Potent preventive action of curcumin on radiation-induced initiation of mammary tumorigenesis in rats. Carcinogenesis , 2000 , 21 : 1835-1841.
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5. Choudhuri T, Pal S, Agwarwal ML, Das T, Sa G. Curcumin in induces apoptosis in human breast cancer cells through p53-dependent Bax induction. FEBS Lett , 2002 , 512: 334-340.
6. Han SS, Chung ST, Robertson DA, Ranjan D, Bondada S. Curcumin causes the growth arrest and apoptosis of B cell lymphoma by downregulation of egr-1, c-myc, bcl-XL, NF-kappaB and P53. Clin Immunol, 1999, 93: 152-161.
7. Jaiswal AS, Marlow BP, Gupta Narayan S.β-Catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin(diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene, 2002 , 21: 8414-8427.
8.吴孝杰,庞江琳,孙显斌,姜黄素及其联合化疗对子宫颈癌Hela细胞体外增殖的影响.华夏医学,2005,18(4):534-536.
9.王菁鹏,林青,姜黄素对子宫颈癌HeLa细胞的抑制作用.现代医药卫生,2006,22(16):2435-2437.
10. Prusty BK,Das BC. Constitutive activation of transcription factor AP-1 in cervical cancer and suppression of human papillomavirus (HPV) transcription and AP-1 activityin HeLa cells by curcumin. Int J Cancer,2005,113(6):951-960
11. Banuelos A ,Reyes E ,Ocadiz R ,Alvarez E, Moreno M, Monroy A, Gariqlio P. Neocarzinostatin induces an effective p53-dependent response in human papillomavirus positive cervical cancer cells . J Pharmacol Exp Ther , 2003 ,306 (2) :671-680.
12. Herington CS. Human papillomaviruses and cervical neoplasia : interacion of HPV with other factors. J Clin Pathol , 1995 ,48 :1-6.
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