Effects of Cdc42 overexpression on the estrogen-enhanced multidrug resistance in breast cancer cells / 中华肿瘤杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the changes of Cdc42 expression under estrogen stimulation, and to explore the signaling pathway of intracellular material transportation caused by estrogen.</p><p><b>METHODS</b>MTT was used to test the drug sensitivity of cells. Real-time PCR was used to evaluate the expression of Cdc42 mRNA. The amount of ADM accumulated in MCF-7 cells was detected by flow cytometry. The protein levels of active-Cdc42 and Total-Cdc42 were measured by Western blot.</p><p><b>RESULTS</b>IC(50) of ADM in MCF-7 cells was increased from (0.098 ± 0.011) µg/ml to (0.134 ± 0.130) µg/ml (P < 0.05) after estrogen stimulation. The amount of ADM accumulated in MCF-7 cells was reduced from 7.253 ± 0.310 to 3.233 ± 0.313 (P < 0.05). All of Cdc42 mRNA, active-Cdc42 protein and total-Cdc42 protein were increased (P < 0.05). After the treatment with siRNA, the IC(50) of ADM in siRNA group was decreased to (0.057 ± 0.017) µg/ml (P < 0.05) compared with that in the control group. The amount of accumulated ADM was significantly increased in the siRNA group, and all the expression levels of Cdc42 mRNA, active-Cdc42 protein and total-Cdc42 protein were decreased in the siRNA group (P < 0.05).</p><p><b>CONCLUSIONS</b>Estrogen enhances the drug resistance in breast cancer cells. The mechanism of this effect may be via the enhancing Cdc42 expression and decreasing the accumulation of chemotherapeutic drugs in the cancer cells.</p>