p,p′-DDT对乳腺癌细胞MCF-7黏附能力及黏附分子的影响
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摘要
目的探讨有机氯残留物有效成分p,p′-DDT对乳腺癌细胞MCF-7黏附能力及黏附分子的影响。方法将10~(-7)mol/L的p,p′-DDT作用于MCF-7 48h后,分别采用细胞聚集试验和结晶紫染色法分析其对MCF-7细胞间黏附率和细胞与基质间黏附率的影响,并采用RT-q PCR法和Western blot法检测MCF-7中钙黏附蛋白E(E-cadherin)和CD29 mRNA和蛋白表达水平。结果 10~(-7)mol/L的p,p′-DDT作用MCF-7 48h后,MCF-7细胞间黏附率明显降低,细胞与基质间黏附率明显升高;同时下调了E-cadherin mRNA和蛋白表达水平,上调了CD29 mRNA和蛋白表达水平。结论 p,p′-DDT具有降低MCF-7细胞间黏附并提高细胞与基质黏附的作用。p,p′-DDT可能通过改变黏附关键因子E-cadherin和CD29的表达来影响细胞黏附,进而促进肿瘤细胞的侵袭、转移。
Objective To investigate the effect of p,p′-DDT on the adhesion of breast cancer cells and its molecular mechanism. Methods The breast cancer MCF-7 cells were treated with 10~(-7) mol/L p,p′-DDT for 48 h. The cell-to-cell adhesion analysis and cell-to-matrix adhesion analysis were performed; the expression of E-cadherin and CD29 mRNA and protein in MCF-7 cells was detected by q RT-PCR and Western blot, respectively. Results The cell-to-cell adhesion rate was significantly decreased, and cell-to-matrix adhesion rate was increased in MCF-7 cells treated with p,p′-DDT. The Transwell migration and invasion assays revealed that p,p ′-DDT enhanced the ability of migration and invasion of MCF-7 cells. The expression of E-cadherin was down-regulated, while CD29 expression level was up-regulated in MCF-7 cells after p,p′-DDT treatment. Conclusion The p,p′-DDT can reduce cell-to-cell adhesion and enhance cell-to-matrix adhesion of breast cancer MCF-7 cells, which may be associated with the alteration of the expression of key adhesion factors E-cadherin and CD29, resulting in the invasion and metastasis of tumor cells.
Objective To investigate the effect of p,p′-DDT on the adhesion of breast cancer cells and its molecular mechanism. Methods The breast cancer MCF-7 cells were treated with 10~(-7) mol/L p,p′-DDT for 48 h. The cell-to-cell adhesion analysis and cell-to-matrix adhesion analysis were performed; the expression of E-cadherin and CD29 mRNA and protein in MCF-7 cells was detected by q RT-PCR and Western blot, respectively. Results The cell-to-cell adhesion rate was significantly decreased, and cell-to-matrix adhesion rate was increased in MCF-7 cells treated with p,p′-DDT. The Transwell migration and invasion assays revealed that p,p ′-DDT enhanced the ability of migration and invasion of MCF-7 cells. The expression of E-cadherin was down-regulated, while CD29 expression level was up-regulated in MCF-7 cells after p,p′-DDT treatment. Conclusion The p,p′-DDT can reduce cell-to-cell adhesion and enhance cell-to-matrix adhesion of breast cancer MCF-7 cells, which may be associated with the alteration of the expression of key adhesion factors E-cadherin and CD29, resulting in the invasion and metastasis of tumor cells.
引文
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[4]Cohn BA,La MM,Krigbaum NY,et al.DDT Exposure in Utero and Breast Cancer[J].Journal of Clinical Endocrinology&Metabolism,2015,100(8):2865-2872.DOI:10.1210/jc.2015-1841.
[5]胡大为,杨景哲.有机氯农药暴露与乳腺癌[J].肿瘤学杂志,2014,20(4):286-289.DOI:10.11735/j.issn.1671-170X.2014.04.B005.
[6]Peng SY,Tu HF,Yang CC,et al.miR-134 targets PDCD7 to reduce E-cadherin expression and ehnace oral cancer progression[J].Int JCancer,2018,143(11):2892-2904.DOI:10.1002/ijc.31638.
[7]Nakano Doi A,Sakuma R,Matsuyama T,et al.Ischemic stroke activates the VE-cadherin promoter and increases VE-cadherin expression in adult mice[J].Histol Histopathol,2018,33(5):507-521.DOI:10.14670/HH-11-952.
[8]吕凤,郭晓静,付丽.整合素表达变化在乳腺癌发生及发展中的作用研究进展[J].中华病理学杂志,2015,44(4):294-296.DOI:10.3760/cma.j.issn.0529-5807.
[9]何力,林秀峰.miR-183靶向TBX3调控PTEN通路对乳腺癌生物学行为影响[J].中华肿瘤防治杂志,2017,24(7):451-457.DOI:10.16073/j.cnki.cjcpt.2017.07.004.
[10]Servent A,Benistant C,Pannequin J,et al.Src family tyrosine kinases-driven colon cancer cell invasion is induced by Csk membrane delocalization[J].Oncogene,2010,29(9):1303-1315.DOI:10.1038/onc.2009.450.
[11]Mustafa MD,Banerjee BD,Ahmed RS,et al.Gene-environment interaction in preterm delivery with special reference to organochlorinepesticides[J].Mol Hum Reprod,2013,19(1):35-42.DOI:10.1093/molehr/gas039.
[12]赵君宇,刘建新,晋小婷,等.p,p'-DDT对大肠癌细胞DLD1细胞黏附的影响[J].安全与环境学报,2014,2:289-293.DOI:10.13637/j.issn.1009-6094.
[13]Liu Y,Wang Y,Zhang Y,et al.Abnormal expression of p120-catenin,E-cadherin,and small GTPases is significantly associated with malignant phenotype of human lung cancer[J].Lung Cancer,2009,63(3):375-382.DOI:10.1016/j.lungcan.2008.12.012.
[14]Frixen UH,Behrens J,Sachs M,et al.E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells[J].Journal of Cell Biology,2013,125(1):173-185.
[15]He X,Dong X,Zou D,et al.Enantioselective Effects of o,p'-DDT on Cell Invasion and Adhesion of Breast Cancer Cells:Chirality in Cancer Development[J].Environmental Science&Technology,2015,49(16):10028-10037.DOI:10.1021/acs.est.5b02147.