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F 3.85mm Megapixel 10x Digital Zoom Download Driver.647 – directly obtained from the manufacturer.Thioredoxin-1 regulates the cellular uptake of docetaxel in human androgen-independent prostate cancer cells.
Resistance to chemotherapy is the main reason for the failure of cancer treatment. Thioredoxin-1 (TRX-1) is a redox-regulating protein that plays important roles in maintaining intracellular homeostasis and cell growth, including development, cell proliferation, differentiation and apoptosis. However, the contribution of TRX-1 to chemotherapy resistance has not been elucidated. We investigated the relationship between TRX-1 and doxorubicin or docetaxel (DCT) resistance in prostate cancer (CaP) cells. The potential role of TRX-1 in the cellular uptake of DCT was also investigated. The expression of TRX-1 in CaP was examined by RT-PCR and immunohistochemistry. Expression of TRX-1 in CaP cells with or without DCT treatment was measured by Western blot analysis and real-time PCR. The intracellular concentration of DCT was measured by high performance liquid chromatography. Uptake of DCT was visualized by the 5,6-carboxy-2′,7′-dichlorofluorescein diacetate assay and directly measured by flow cytometry. Furthermore, the protein levels of TRX-1 and Bcl-2 in CaP cells were determined after transfection with siRNA against TRX-1 or inhibitor against Bcl-2. We found that the expression level of TRX-1 was significantly lower in human CaP cells compared to normal prostate cells. TRX-1 was present in CaP cells and was decreased with DCT treatment. TRX-1 knockdown significantly inhibited the uptake of DCT in CaP cells, but exogenous TRX-1 expression enhanced the uptake. TRX-1 knockdown decreased the expression of Bcl-2 and activation of Bax. TRX-1 and Bcl-2 also showed an inverse relationship in CaP cells. Moreover, TRX-1 expression was negatively correlated with the clinical stage and PSA level, whereas it was positively correlated with Bcl-2 expression and Bax activity. These results suggest that TRX-1 may regulate the cellular uptake of DCT in CaP cells through the Bcl-2/Bax-
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