三苯氧胺对乳腺癌细胞凋亡和耐药性的影响

目的　观察雌激素 (E2 )及三苯氧胺 (tamoxifen ,TAM)对乳腺癌MCF 7细胞凋亡调控基因 (bax、bcl 2 )及多药耐药基因 (mdr 1)的影响。方法　利用免疫组化法及原位杂交法检测MCF 7细胞在E2 和TAM作用后bax、bcl 2及mdr 1基因的变化。结果　E2 可以明显刺激bcl 2和mdr 1基因表达 ,而TAM则可使其降低。首次利用人工合成的bax寡聚脱氧核苷酸探针 ,对肿瘤细胞内baxmRNA进行原位杂交 ,显示baxmRNA可被E2 下调 ,但在TAM作用下明显升高。相关性分析显示 ,bcl 2和mdr 1基因之间在TAM作用后有相关性 (r=0 6 ,P <0 0 5 )。结论　TAM在乳癌内分泌治疗中不仅可调节肿瘤细胞凋亡 ,也可降低肿瘤细胞耐药性 ,抗凋亡基因bcl 2和多药耐药性之间有密切的功能联系 ,对其深入研究将有助于肿瘤内分泌治疗的进展。

Effect of tamoxifen on apoptosis and drug resistance of breast cancer cells in vitro

Objective To study the effect of estradiol (E 2) and tamoxifen (TAM) on the apoptosis regulatory genes (bax, bcl 2) and mdr 1 in MCF 7 cells. Methods Immunohistochemistry, in situ hybridization were used to observe the changes in bax, bcl 2 and mdr 1 genes after treatment with E 2 and TAM. Results E 2 had ability to increase the expression of bcl 2 and mdr 1 but TAM decrease the expression of both. Synthetic bax oligodeoxynucleotide (ODN) was used as probe to perform in situ hybridization. It was shown that bax mRNA in MCF 7 cells was down regulated by E 2 and up regulated by TAM. Significant correlation between bcl 2 and mdr 1 was observed after TAM treatment of MCF 7 cells ( P <0 05). Conclusion TAM regulates cell apoptosis and inhibits development of drug resistance of MCF 7 breast cancer.