Résumé
Aldo-keto reductase family 1 member C3 has recently been regarded as a potential therapeutic target in castrate-resistant prostate cancer. Herein, we investigated whether berberine delayed the progression of castrate-resistant prostate cancer by reducing androgen synthesis through the inhibition of Aldo-keto reductase family 1 member C3. Cell viability and cellular testosterone content were measured in prostate cancer cells. Aldo-keto reductase family 1 member C3 mRNA and protein level were detected by RT-PCR and Western bolt analyses, respectively. Computer analysis with AutoDock Tools explored the molecular interaction of berberine with Aldo-keto reductase family 1 member C3. We found that berberine inhibited 22Rv1 cells proliferation and decreased cellular testosterone formation in a dose-dependent manner. Berberine inhibited Aldo-keto reductase family 1 member C3 enzyme activity, rather than influenced mRNA and protein expressions. Molecular docking study demonstrated that berberine could enter the active center of Aldo-keto reductase family 1 member C3 and form p-p interaction with the amino-acid residue Phe306 and Phe311. In conclusion, the structural interaction of berberine with Aldo-keto reductase family 1 member C3 is attributed to the suppression of Aldo-keto reductase family 1 member C3 enzyme activity and the inhibition of 22Rv1 prostate cancer cell growth by decreasing the intracellular androgen synthesis. Our result provides the experimental basis for the design, research, and development of AKR1C3 inhibitors using berberine as the lead compound.
Résumé
Objective To explore the value of AKRIBIO combined with GPC-3 in improving the sensitivity and specificity of immunohistochemical diagnosis of hepatocellular carcinoma (HCC). Methods The microarray including 75 HCC and adjacent tissues was subjected to immunohistochemistry detection of AKRIBIO and GPC-3 expression. A Logistic regression diagnostic model was established using the results of tissue microarray (training group). The ROC curves (the receiver-operating characteristic curve) and area under the curve (AUC) were used to evaluate the sensitivity and specificity of AKRIBIO, GPC-3 or their combination. The Logistic regression diagnostic model was validated with 200 HCC and adjacent tissues (testing group). Results For the training group, the AUC values of AKRIBIO, GPC-3, and AKRIBIO combined with GPC-3 were 0. 773, 0. 800, and 0. 931, respectively. The sensitivity of AKRIBIO and GPC-3 were 56% and 61. 3%, respectively, and their specificity was both 98. 7%. AKRIBIO combined with GPC-3 yielded a sensitivity of 88. 0% and a specificity of 97. 3%. For the testing group, sensitivity and specificity of AKRIBIO combined with GPC-3 were 97. 0% and 96. 5%, respectively. Conclusion AKRIBIO combined with GPC-3 can greatly improve the sensitivity and specificity of HCC immunohistochemical diagnosis, and it should be used when necessary in addition to the routine pathological assessment.