| 巩思嘉 林艳 李晓曦 周素瑾 赵正刚 赖姨梅 师惠 丁宁 李芳红 赵子建△.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[J].,2016,16(24):4601-4604 |
| 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 HumanProstate Cancer PC-3 Cells and Xenografts in Nude Mice |
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| DOI： |
| 中文关键词: 前列腺癌 ZL-n-91 PC-3 移植瘤 |
| 英文关键词: Prostate cancer ZL-n-91 PC-3 cells Xenograft tumor |
| 基金项目:国家重大科学研究计划项目（2013CB945200）；江苏省自然科学基金项目（BK20130059, BK2011766）；
国家自然科学基金项目（81372798,81200570）；江苏省高校自然科学研究计划项目（12KJB310006） |
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| 中文摘要: |
| 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（10，50，100，200 uM）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100，200 uM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。 |
| 英文摘要: |
| 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
uM ) 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).Conclusion: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. |
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