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目的探讨Klotho逆转乳腺癌紫杉醇耐药的分子机制。方法 Western blot法检测乳腺癌细胞MCF-7与紫杉醇耐药的乳腺癌细胞MCF-7/PTX中Klotho的表达情况,MTT法检测Klotho对MCF-7/PTX细胞紫杉醇耐药的影响;Western blot法考查Klotho与自噬抑制剂3-methyladenine(3-MA)对MCF-7/PTX细胞Beclin1蛋白表达的影响,并利用MTT法检测Klotho与3-MA对该细胞紫杉醇耐药的影响。结果 MCF-7/PTX细胞中Klotho的表达较MCF-7细胞低,Klotho可增强MCF-7/PTX细胞对紫杉醇的敏感性;MCF-7/PTX细胞中Beclin1表达较MCF-7细胞高,而Klotho与3-MA均可降低该细胞中Beclin1的表达,且Klotho对该细胞紫杉醇耐药的逆转作用与3-MA相仿。结论乳腺癌细胞的紫杉醇耐药与Klotho表达有关,Klotho可通过抑制自噬进而逆转乳腺癌紫杉醇耐药。
Objective To investigate the molecular mechanism of Klotho reversing paclitaxel resistance in breast cancer. Methods The expression of Klotho in breast cancer cells MCF-7 and paclitaxel-resistant breast cancer cells MCF-7 / PTX was detected by Western blot. The effect of Klotho on paclitaxel resistance in MCF-7 / PTX cells was detected by MTT assay. To investigate the effect of Klotho and autophagy inhibitor 3-methyladenine on the expression of Beclin1 in MCF-7 / PTX cells. The effect of Klotho and 3-MA on paclitaxel resistance was examined by MTT assay. Results The expression of Klotho in MCF-7 / PTX cells was lower than that in MCF-7 cells. Klotho enhanced the sensitivity of MCF-7 / PTX cells to paclitaxel. The expression of Beclin1 in MCF-7 / PTX cells was higher than that in MCF-7 cells Both Klotho and 3-MA reduced the expression of Beclin1 in this cell, and the reverse effect of Klotho on paclitaxel resistance was similar to that of 3-MA. Conclusions Taxol resistance in breast cancer cells is related to Klotho expression. Klotho can reverse paclitaxel resistance by inhibiting autophagy.