砷及其代谢产物对P21基因表达的影响
|
摘要
目的探讨砷及砷化物对人肺腺癌细胞系A549细胞、云南宣威肺腺癌细胞XWLC-05细胞、人乳腺癌细胞MDAMB-231细胞中的P21基因表达的影响。方法以亚砷酸钠、一甲基砷酸(MMA)、二甲基砷酸(DMA)处理A549细胞、XWLC-05细胞、MDA-MB-231细胞并以荧光定量聚合酶链式反应(q RT PCR)法检测P21mRNA的表达;以不同浓度的亚砷酸钠处理A549细胞、XWLC-05细胞、MDA-MB-231细胞并以q RT PCR法检测P21基因mRNA的表达。结果亚砷酸钠可诱导P21基因mRNA的表达,MMA、DMA不能诱导细胞中P21基因m RNA的表达;不同的亚砷酸浓度处理的细胞,可影响细胞中P21基因mRNA的表达。结论砷可影响细胞中P21基因的表达,并且与剂量存在一定的关系。
[Objective]To investigate the effect of arsenic and arsenide on P21 gene expression in human lung adenocarcinoma cell line A549 cells,Xuanwei lung adenocarcinoma cell line XWLC-05 and human breast cancer cell line MDA-MB-231.[Methods]A549 cells,XWLC-05 cells and MDA-MB-231 cells were treated with sodium arsenite,monomethyl arsenate(MMA)and dimethyl arsenic acid(DMA),and the P21 mRNA expression was detected by Fluorescent Quantitative PCR(qRT PCR).A549 cells,XWLC-05 cells and MDA-MB-231 cells were treated with different concentrations of sodium arsenite and the expression of P21 mRNA was detected by q RT PCR.[Results]The expression of P21 mRNA was induced by sodium arsenite,while MMA and DMA did not induce the expression of P21 mRNA in the cells. Different concentrations of arsenic trioxide treatment could affect the expression of P21 mRNA in cells.[Conclusion] Arsenic can affect the expression of P21 gene in cells,and there is a relationship with dose.
[Objective]To investigate the effect of arsenic and arsenide on P21 gene expression in human lung adenocarcinoma cell line A549 cells,Xuanwei lung adenocarcinoma cell line XWLC-05 and human breast cancer cell line MDA-MB-231.[Methods]A549 cells,XWLC-05 cells and MDA-MB-231 cells were treated with sodium arsenite,monomethyl arsenate(MMA)and dimethyl arsenic acid(DMA),and the P21 mRNA expression was detected by Fluorescent Quantitative PCR(qRT PCR).A549 cells,XWLC-05 cells and MDA-MB-231 cells were treated with different concentrations of sodium arsenite and the expression of P21 mRNA was detected by q RT PCR.[Results]The expression of P21 mRNA was induced by sodium arsenite,while MMA and DMA did not induce the expression of P21 mRNA in the cells. Different concentrations of arsenic trioxide treatment could affect the expression of P21 mRNA in cells.[Conclusion] Arsenic can affect the expression of P21 gene in cells,and there is a relationship with dose.
引文
[1]ECKSTEIN M,ELEAZER R,REA M,et al. Epigenomic reprogramming in inorganic arsenic-mediated gene expression patterns during carcinogenesis[J].Rev Environ Health,2016,32(1):93-103.
[2]STUECKLE TA,LU Y,DAVIS ME,et al. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells[J].Toxicol Appl Pharm,2012,261(2):204-216.
[3]JOCA L,SACKS J D,MOORE D,et al. Systematic review of differential inorganic arsenic exposure in minority,low-income,and indigenous populations in the United States[J/OL].Environ Int,2016,s 92-93:707-715.[2018-03-01]. https://www.ncbi.nlm.nih.gov/pubmed/?term=Systematic+review+of+differential+inorganic+arsenic+exposure+in+minority%2C+low income%2C+and+indigenous+populations+in+the+United+States. DOI:10.1016/j.envint.2016.01.011.
[4]GU S,LAI Y,CHEN H,et al. miR-155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells[J].Sci Rep,2017,7(1):12155.
[5]WANG QQ,ZHOU XY,ZHANG YF,et al. Methylated arsenic metabolites bind to PML protein but do not induce cellular differentiation and PML-RARαprotein degradation[J].Oncotarget,2015,6(28):25646-25659.
[6]SCHMID G,KRAMER MP,MAURER M,et al. Cellular and organismal ageing:Role of the p53 tumor suppressor protein in the induction of transient and terminal senescence[J].J Cell Biochem,2007,101(6):1355-1369.
[7]龚辉,程薇,毛红霞. p21基因对肝癌细胞的生物学影响[J].江西医药,2013,48(2):121-122.
[8]PRAJAPAT V,KALE RK,SINGH RP. Silibinin combination with arsenic strongly inhibits survival and invasiveness of human prostate carcinoma cells[J]. Nutr Cancer,2015,67(4):647-658.
[9]殷秀岩,李昕.砷甲基化代谢及砷中毒发病风险因素研究进展[J].中国公共卫生,2015,31(6):848-852.
[10]KHALEGHIAN A,GHAFFARI SH,AHMADIAN S,et al. Metabolism of arsenic trioxide in acute promyelocytic leukemia cells[J].J Cell Biochem,2014,115(10):1729-1739.
[11]LI Y,WANG D,LI X,et al. A Potential Synergy between Incomplete Arsenic Methylation Capacity and Demographic Characteristics on the Risk of Hypertension:Findings from a Cross-Sectional Study in an Arsenic-Endemic Area of Inner Mongolia,China[J].Int J Environ Res Public Health,2015,12(4):3615-3632.
[12]VAHTER M. Mechanisms of arsenic biotransformation[J/OL].Toxicology,2002,181-182(6):211-217.[2018-03-01].https://www.sciencedirect. com/science/article/pii/S0300483X02002858. DOI:org/10.1016/S0300-483X(02)00285-8.
[13] BANERJEE M,CAREW MW,ROGGENBECK BA,et al. A novel pathway for arsenic elimination:human multidrug resistance protein 4(MRP4/ABCC4)mediates cellular export of dimethylarsinic acid(DMAV)and the diglutathione conjugate of monomethylarsonous acid(MMAIII)[J].Mol Pharmacol,2014,86(2):168-179.
[14]HARPER JW,ADAMI GR,WEI N,et al. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases[J].Cell,1993,75(4):805-816.
[15]HRGOVIC I,DOLL M,KLEEMANN J,et al. The histone deacetylase inhibitor trichostatin a decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p21-dependent pathways[J].BMC Cancer,2016,16(1):763.
[16]LIU YW,XIA R,LU K,et al. LincRNAFEZF1-AS1 represses p21 expression to promote gastric cancer proliferation through LSD1-Mediated H3K4me2 demethylation[J].Mol Cancer,2017,16(1):39.
[17]VALESKY EM,HRGOVIC I,DOLL M,et al. Dimethylfumarate effectively inhibits lymphangiogenesis via p21 induction and G1 cell cycle arrest[J].Exp Dermatol,2016,25(3):200-205.
[18]顾亚琴,张良,杨召聪,等.砷剂抗肿瘤作用研究进展[J].中药药理与临床,2016(1):224-227.
[19] ZHANG P. On arsenic trioxide in the clinical treatment of acute promyelocytic leukemia[J].Leuk Res Rep,2017,7(C):29-32.
[20]CIALFI S,PALERMO R,MANCA S,et al. Loss of Notch1-dependent p21Waf1/Cip1 expression influences the Notch1 outcome in tumorigenesis[J].Cell Cycle,2014,13(13):2046-2245.
[2]STUECKLE TA,LU Y,DAVIS ME,et al. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells[J].Toxicol Appl Pharm,2012,261(2):204-216.
[3]JOCA L,SACKS J D,MOORE D,et al. Systematic review of differential inorganic arsenic exposure in minority,low-income,and indigenous populations in the United States[J/OL].Environ Int,2016,s 92-93:707-715.[2018-03-01]. https://www.ncbi.nlm.nih.gov/pubmed/?term=Systematic+review+of+differential+inorganic+arsenic+exposure+in+minority%2C+low income%2C+and+indigenous+populations+in+the+United+States. DOI:10.1016/j.envint.2016.01.011.
[4]GU S,LAI Y,CHEN H,et al. miR-155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells[J].Sci Rep,2017,7(1):12155.
[5]WANG QQ,ZHOU XY,ZHANG YF,et al. Methylated arsenic metabolites bind to PML protein but do not induce cellular differentiation and PML-RARαprotein degradation[J].Oncotarget,2015,6(28):25646-25659.
[6]SCHMID G,KRAMER MP,MAURER M,et al. Cellular and organismal ageing:Role of the p53 tumor suppressor protein in the induction of transient and terminal senescence[J].J Cell Biochem,2007,101(6):1355-1369.
[7]龚辉,程薇,毛红霞. p21基因对肝癌细胞的生物学影响[J].江西医药,2013,48(2):121-122.
[8]PRAJAPAT V,KALE RK,SINGH RP. Silibinin combination with arsenic strongly inhibits survival and invasiveness of human prostate carcinoma cells[J]. Nutr Cancer,2015,67(4):647-658.
[9]殷秀岩,李昕.砷甲基化代谢及砷中毒发病风险因素研究进展[J].中国公共卫生,2015,31(6):848-852.
[10]KHALEGHIAN A,GHAFFARI SH,AHMADIAN S,et al. Metabolism of arsenic trioxide in acute promyelocytic leukemia cells[J].J Cell Biochem,2014,115(10):1729-1739.
[11]LI Y,WANG D,LI X,et al. A Potential Synergy between Incomplete Arsenic Methylation Capacity and Demographic Characteristics on the Risk of Hypertension:Findings from a Cross-Sectional Study in an Arsenic-Endemic Area of Inner Mongolia,China[J].Int J Environ Res Public Health,2015,12(4):3615-3632.
[12]VAHTER M. Mechanisms of arsenic biotransformation[J/OL].Toxicology,2002,181-182(6):211-217.[2018-03-01].https://www.sciencedirect. com/science/article/pii/S0300483X02002858. DOI:org/10.1016/S0300-483X(02)00285-8.
[13] BANERJEE M,CAREW MW,ROGGENBECK BA,et al. A novel pathway for arsenic elimination:human multidrug resistance protein 4(MRP4/ABCC4)mediates cellular export of dimethylarsinic acid(DMAV)and the diglutathione conjugate of monomethylarsonous acid(MMAIII)[J].Mol Pharmacol,2014,86(2):168-179.
[14]HARPER JW,ADAMI GR,WEI N,et al. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases[J].Cell,1993,75(4):805-816.
[15]HRGOVIC I,DOLL M,KLEEMANN J,et al. The histone deacetylase inhibitor trichostatin a decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p21-dependent pathways[J].BMC Cancer,2016,16(1):763.
[16]LIU YW,XIA R,LU K,et al. LincRNAFEZF1-AS1 represses p21 expression to promote gastric cancer proliferation through LSD1-Mediated H3K4me2 demethylation[J].Mol Cancer,2017,16(1):39.
[17]VALESKY EM,HRGOVIC I,DOLL M,et al. Dimethylfumarate effectively inhibits lymphangiogenesis via p21 induction and G1 cell cycle arrest[J].Exp Dermatol,2016,25(3):200-205.
[18]顾亚琴,张良,杨召聪,等.砷剂抗肿瘤作用研究进展[J].中药药理与临床,2016(1):224-227.
[19] ZHANG P. On arsenic trioxide in the clinical treatment of acute promyelocytic leukemia[J].Leuk Res Rep,2017,7(C):29-32.
[20]CIALFI S,PALERMO R,MANCA S,et al. Loss of Notch1-dependent p21Waf1/Cip1 expression influences the Notch1 outcome in tumorigenesis[J].Cell Cycle,2014,13(13):2046-2245.