染料木黄酮抑制AKR1C3抗去势抵抗前列腺癌的生长及其机制研究

目的:研究植物雌激素染料木黄酮（GEN）抑制AKR1C3的表达，进而抑制去势抵抗前列腺癌（CRPC）的生长，为染料木黄酮临床治疗CRPC提供理论依据。方法:在无激素的血清环境下培养22RV1、VCaP、RWPE-1细胞，以不同浓度（0、12.5、25、50、100 μmol/L）的GEN处理48 h。利用CCK-8检测细胞增殖活性。通过AKR1C3 siRNA、AKR1C3抑制剂（ASP-9521）分别与GEN联合干扰22RV1、VCaP细胞，用Western blot检测细胞中PSA及AKR1C3蛋白的表达水平。结果:染料木黄酮能抑制去势抵抗前列腺癌的生长。Western blot结果显示，GEN能够抑制PSA、AKR1C3蛋白的表达，且与AKR1C3 siRNA、AKR1C3抑制剂（ASP-9521）联合作用时，对AKR1C3的抑制效果更为显著。结论:染料木黄酮可能通过抑制去势抵抗前列腺癌细胞中AKR1C3的表达，进而抑制CRPC细胞的增殖。

Genistein Inhibits the Growth of AKR1C3 Anti-castration Resistance Prostate Cancer and Its Mechanism

Objective: To study the inhibition of akr1c3 expression by phytoestrogen genistein(Gen), thereby inhibiting the growth of castration-resistant prostate cancer(CRPC), and provide a theoretical basis for the clinical treatment of CRPC with genistein. Methods: 22RV1, VCaP, RWPE-1 cells were cultured in a hormone-free serum environment, and treated with different concentrations (0, 12.5, 25, 50, 100) μmol/L of GEN for 48 h. CCK-8 was used to detect cell proliferation activity. AKR1C3 siRNA and AKR1C3 inhibitor(ASP-9521) were combined with GEN to interfere with 22RV1 and VCaP cells, respectively, and the expression levels of PSA and AKR1C3 proteins in the cells were detected by Western blot. Results: Genistein could inhibit castration and resist the growth of prostate cancer. Western blot results showed that GEN could inhibit the expression of PSA and AKR1C3 proteins, and when combined with AKR1C3 siRNA and AKR1C3 inhibitor (ASP-9521), the inhibitory effect on AKR1C3 was more significant. Conclusion: Genistein expression in prostate cancer cells can resist by inhibiting AKR1C3 castration, thereby inhibiting cell proliferation CRPC.