选择性磷酸二酯酶4抑制剂ZL-n-91对人前列腺癌PC-3细胞和裸鼠移植瘤的影响

Effects of a Selective Phosphodiesterase 4 Inhibitor, ZL-n-91, on the Human Prostate Cancer PC-3 Cells and Xenografts in Nude Mice

目的：研究选择性磷酸二酯酶4抑制剂ZL-n-91对人前列腺癌PC-3细胞人前列腺癌PC-3细胞和裸鼠移植瘤的影响。方法：将不同浓度的ZL-n-91（10,50,100,200μM）分别处理体外培养的前列腺癌PC-3细胞24 h和48 h,用CCK-8法测定ZL-n-91对前列腺癌PC-3细胞增殖的影响;将人前列腺癌PC-3细胞皮下种植裸鼠,待瘤体积达到100-200 mm3,口服ZL-n-91,定期测定动物体重、肿瘤体积、肿瘤重量、计算抑瘤率;采用免疫组织化学检测肿瘤组织Ki67的表达。结果：ZL-n-91能抑制PC-3细胞的增殖,药物浓度为100,200μM时,作用24 h后其抑制率分别达23.7%、58.1%,作用48 h后其抑制率分别达36.5%、70%。与对照组比较差异有统计学意义（P〈0.001）,并且其抑制增殖作用呈浓度和时间依赖性。荷瘤裸鼠经ZL-n-91治疗12天开始,给药组小鼠肿瘤体积明显小于对照组（P〈0.05）,给药32天时,给药组肿瘤体积和重量约为对照组的1/2倍,其抑瘤率高达45.96%;免疫组化检测肿瘤组织中Ki67的表达,定量分析对照组和给药组阳性率分别为（40.7±0.18）%和（18.11±0.06）%,结果显示给药组小鼠肿瘤的增殖明显弱于对照组（P〈0.001）。结论：ZL-n-91对人前列腺癌PC-3细胞及移植瘤的生长有明显的抑制作用。

Objective： To explore the effects of ZL-n-91, a selective phosphodiesterase 4 inhibitor, on the growth of human prostate cancer PC-3 cells and its subcutaneous xenograft in nude mice. Methods： Different concentrations of ZL-n-91 （10, 50, 100, 200 μM ） were applied in cultured prostate cancer cells, PC-3, for 24 h and 48 h. The effects of ZL-n-91 on the growth of PC-3 cells were detected by CCK-8 assay. Nude mice xenograft models were established with PC-3 cells, and the mice were randomly divided into 2 groups and the drug or the dissolving solution was administrated daily for 32 days. Tumor sizes were measured twice every week. In the end, body weight, tumor weight, tumor volume were also measured. The pathology of tumor tissues was also analyzed. Finally, immunohistochemistry was performed to evaluate the levels of Ki67 in tumor tissues. Results： ZL-n-91 could inhibit the proliferation of cultured PC-3 cells. The inhibitory effects were time and dosage dependent （P〈0.001）. In xenograft mice, the average tumor volume in ZL-n-91 treated group was significantly smaller than that of the control group （P 〈 0.05） at the end of observation. Tumor weight in ZL-n-91 treated group was also significantly lower compared to the control group （P 〈 0.05） with the suppression rate at 45.96 %. Positive staining of Ki67 in ZL-n-91 treated group （18.11 ± 0.06） % was much less than that of control group （40.7 ± 0.18） % （P 〈 0.001）. Conclusions： ZL-n-91 can inhibit the proliferation of prostate cancer PC-3 cells and suppress the growth of PC-3 subcutaneous xenografts in nude mice.