PDK1 Overexpression Attenuates Drug Sensitivity of Tamoxifen Resistant Breast Cancer Cells
GAN Delu, JIANG Yulin, YUE Shujun, QIAN Husun, ZHOU Ting, ZHANG Dian, SHI He, FANG Wenli, YAO Mengli, CHEN Tingmei*
This article explored the correlation and mechanism of PDK1 and tamoxifen resistance in breast cancer cells. The levels of PDK1, p-AKT, AKT, p-mTOR, and mTOR in breast cancer MCF-7 and T47D cells as well as tamoxifen-resistant MCF-7R and T47DR cells were detected by Western blot. The levels of PDK1 in cells were changed by transfection, perifosine and dichloroacetic acid treatments, and then the changes of C-myc, CyclinD1, Bcl-2 and Bcl-xl levels were detected by Western blot. The cell proliferation was detected by CCK-8, and the cell apoptosis was detected by FCM. The results showed that, as compared with MCF-7 or T47D cells, the protein levels of PDK1 significantly increased in MCF-7R and T47DR cells. After the transfection of PDK1-siRNA into MCF-7R and T47DR cells, the IC50 of OHT and proliferations of drug-resistant cells significantly reduced. The PI3K/AKT/mTOR pathway was activated, which up-regulated the expression of PDK1 in tamoxifen-resistant breast cancer cells. Interfering with the expression of PDK1, and combinatory treatment with perifosine and di-chloroacetic acid inhibited the proliferation and promoted the apoptosis of tamoxifen-resistant cells. This study provides a new idea for the clinical treatment of tamoxifen-resistant breast cancer.
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