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目的研究11β-羟基类固醇脱氢酶2型基因(11β-HSD 2)表达在癌症发生及预防过程中的变化,探讨该基因作为葡萄籽提取物(GSE)抑制乳腺上皮细胞慢性癌变过程中靶点的可能性。方法建立低浓度致癌物NNK和B[a]P刺激乳腺上皮细胞MCF 10A癌变及GSE抑制乳腺上皮细胞癌变过程的细胞模型,研究瞬时转染了靶向11β-HSD 2基因的小RNA后的癌变细胞的生物学特性改变,并用Western blot分析11β-HSD 2基因在癌变细胞和经GSE抑制后细胞中的表达情况。结果使用靶向11β-HSD 2基因的小RNA抑制后的癌变细胞,在低生长因子培养基中形成细胞集落的能力降低,与正常乳腺上皮细胞相当。11β-HSD 2基因在致癌物慢性刺激的细胞中呈现高表达,而在正常乳腺上皮细胞和经GSE与致癌物联合处理的细胞中基本不表达或表达水平很低。结论抑制癌变细胞中11β-HSD 2基因的表达可使细胞的生物学表现趋于正常,GSE抑制细胞癌变的机制可能是通过抑制11β-HSD 2基因的表达实现,11β-HSD 2基因可能是GSE抑制乳腺上皮细胞癌变的分子靶点。
Objective To investigate the expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD 2) in the pathogenesis and prevention of cancer, and to investigate the role of this gene as a target in the inhibition of chronic carcinogenesis of breast epithelial cells by grape seed extract (GSE) The possibility of. Methods The cell models of carcinogenesis of mammary epithelial cells MCF 10A stimulated by low concentrations of carcinogens NNK and B [a] P and the inhibition of GSE on the carcinogenesis of breast epithelial cells were established. The carcinogenesis of small interfering RNAs targeting 11β-HSD 2 gene was transiently transfected The biological characteristics of the cells were changed. The expression of 11β-HSD 2 gene in cancerous cells and GSE-suppressed cells was analyzed by Western blot. Results The use of small RNA-suppressed cancerous cells targeting the 11β-HSD 2 gene reduced the ability to form cell colonies in low growth medium, comparable to normal mammary epithelial cells. The 11β-HSD 2 gene is highly expressed in cells that are chronically stimulated by carcinogens, but is not expressed or expressed at a very low level in normal mammary epithelial cells and cells treated with GSE and carcinogens. Conclusion Inhibition of the expression of 11β-HSD 2 in cancerous cells may lead to the normalization of the biological behavior of cells. The mechanism of GSE inhibiting the carcinogenesis may be through inhibiting the expression of 11β-HSD 2 gene. The 11β-HSD 2 gene may be GSE Molecular target of inhibiting the carcinogenesis of breast epithelial cells.