染料木黄酮增强阿比特龙抑制去势抵抗前列腺癌细胞22RV1效应研究

Genistein enhances the anti-castration effect of abiraterone against prostate cancer cell 22RV1

目的研究染料木黄酮增强阿比特龙对去势抵抗前列腺癌(CRPC)细胞的影响及其机制。方法将CRPC细胞株22RV1作为体外细胞模型,染料木黄酮和阿比特龙单独或联合使用时,采用MTT比色法及免疫细胞化学法检测癌细胞的活力及抗原Ki-67表达,反映其增殖情况;通过Western blot检测前列腺癌特异性抗原(PSA)、兔抗人增殖细胞核抗原(PCNA)和酶AKR1C3、CYP17A1的表达水平;通过ELISA实验法检测染料木黄酮与阿比特龙联合作用对22RV1细胞裂解液中睾酮水平的影响。结果MTT检测结果显示,染料木黄酮和阿比特龙单独或联合使用时,在体外对CRPC细胞株22RV1细胞活力具有抑制作用(P<0.05);与单独使用阿比特龙比较,染料木黄酮能增强阿比特龙对22RV1细胞的抑制作用(P<0.05);免疫细胞化学法检测结果显示染料木黄酮能增强阿比特龙的抗肿瘤效果,减弱抗原Ki-67的表达。但Western blot结果显示CYP17A1的表达并未明显减弱,PSA、PCNA和AKR1C3的表达随染料木黄酮浓度的增加逐渐下调。ELISA法检测睾酮水平未明显下降。结论染料木黄酮可增强阿比特龙在体外对去势抵抗前列腺癌细胞的抑制作用,降低PSA、PCNA和AKR1C3及抗原Ki-67的表达。

Objective To investigate the effect and mechanism of genistein flavone on the castrated resistance of abiraterone to prostate cancer cells.Methods Using CRPC cell line 22RV1 as an in vitro cell model,when genistein and abiraterone were used alone or in combination,MTT colorimetry and immunocytochemistry were used to detect the viability of cancer cells and the expression of antigen Ki-67 to reflect their proliferation;The expression levels of PSA,PCNA,AKR1C3 and CYP17A1 were detected by Western blot;the combined effect of genistein and abiraterone on the level of testosterone in 22RV1 cell lysate was detected by ELISA.Results MTT test results showed that genistein and abiraterone,when used alone or in combination,can inhibited the viability of the CRPC cell line 22RV1 in vitro(P<0.05);compared with abiraterone alone,genistein could enhance the inhibitory effect of abiraterone on 22RV1 cells(P<0.05);the results of immunocytochemical detection showed that genistein could enhance the expression of abiraterone and weaken the antigen Ki-67.However,Western blot results showed that the expression of CYP17A1 was not significantly weakened,and the expression of PSA,PCNA and AKR1C3 gradually decreased with the increase of genistein concentration.The testosterone level detected by ELISA did not decrease significantly.Conclusion Genistein can enhance the inhibitory effect of abiraterone on castration-resistant prostate cancer cells in vitro,and reduce the expression of PSA,PCNA,AKR1C3 and antigen Ki-67.