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LXRα可以抑制包括乳腺癌在内的多种肿瘤细胞的增殖,而这种抑制作用的具体机制尚不明了.因此本文探讨了LXRα、NF-κB p65和cyclin D1三者在人乳腺癌细胞增殖中的差异表达.首先采用免疫组化法检测了乳腺癌及癌旁组织中LXRα,NF-κB p65和cyclin D1的表达,结果表明,3种蛋白主要表达于细胞核,且NF-κB p65和cyclin D1在癌组织中的表达显著高于癌旁组织,而LXRα则在癌组织中表达显著降低.用MTT和Western blot检测TO901317对乳腺癌细胞增殖及3种蛋白表达的影响,结果显示,随着TO901317浓度的增加与时间的延长,其对细胞增殖的抑制作用逐渐增强,与此同时能上调LXRα的表达,并下调NF-κB p65和cyclin D1的表达.进一步通过RNA干扰技术下调LXRα的表达,以及应用NF-κB抑制剂PDTC观察TO901317上述作用的改变,发现LXRαsiR NA显著降低TO901317对3种蛋白表达的影响和对细胞增殖的抑制作用.而PDTC则加强TO901317的上述作用效果,除了几乎不影响LXRα的表达外.综上所述,LXRα/NF-κB p65/cyclin D1在乳腺癌细胞增殖中具有重要作用,有助于进一步明确LXRα为新的乳腺癌调控靶点,为今后乳腺癌的分子靶向治疗提供新的思路.
LXRα can inhibit the proliferation of a variety of tumor cells including breast cancer, and the specific mechanism of this inhibition is not clear.Therefore, we investigated the expression of LXRα, NF-κB p65 and cyclin D1 in human breast cancer cell proliferation The expression of LXRα, NF-κB p65 and cyclin D1 in breast cancer tissues and paracancerous tissues was detected by immunohistochemistry.The results showed that the three proteins were mainly expressed in the nucleus and the expressions of NF-κB p65 and cyclin D1 The expression of LXRα in cancer tissues was significantly lower than that in adjacent tissues.Western blot and MTT were used to detect the effect of TO901317 on the proliferation of breast cancer cells and the expression of three proteins.The results showed that with the expression of TO901317 The increase of concentration and time prolong the inhibitory effect of LXRα on cell proliferation, and up-regulate the expression of LXRα and down-regulate the expressions of NF-κB p65 and cyclin D1, further down-regulate LXRα expression by RNA interference and The effect of TO901317 on NF-κB inhibitor PDTC was observed and it was found that LXRαsiR NA significantly reduced the effect of TO901317 on the expression of three proteins and inhibited cell proliferation, while PDTC enhanced TO901317 In addition, the effect of LXRαand LXRαhad no effect on the expression of LXRα.In summary, LXRα / NF-κB p65 / cyclin D1 plays an important role in the proliferation of breast cancer cells, which is helpful to further clarify that LXRα is a new breast cancer Regulation and control targets for molecular targeted therapy for breast cancer in the future to provide new ideas.