蝎毒多肽提取物对非激素依赖性前列腺癌细胞增殖抑制作用的实验研究

目的观察蝎毒多肽提取物(PESV)对非激素依赖性前列腺癌细胞DU145和PC3的生长与增殖、细胞周期及cyclinE和p27蛋白表达的影响。方法采用噻唑蓝(MTT)法检测PESV对前列腺癌细胞PC3和DU145生长与增殖的影响,流式细胞术观察药物对细胞周期的影响,免疫组织化学法检测药物干预后,cyclinE和p27蛋白水平表达的变化。结果MTT结果显示,PBSV40～200mg·L-1时对前列腺癌细胞具有毒性作用,40mg·L-1时,DU145和PC3细胞抑制率(IR)分别为30.5%和33.1%,与阴性组比较细胞增殖抑制作用明显(P<0.05),随剂量加大作用增大,至200mg·L-1时,几乎100%抑制,呈明显剂量效应关系;流式细胞术显示,PESV干预后处于S期的细胞减少(DU145细胞和PC3细胞S期的比例分别为34.1%和17.1%,与阴性对照组相比,P<0.01),处于G0/G1和G2/M期的细胞增多;免疫组织化学检测显示,PBMV干预后,DU145和PC3细胞cyclinE蛋白阳性表达细胞数量减少,灰度值明显下调(P<0.01),p27蛋白阳性表达数量增加,灰度值明显上调(P<0.05)。结论PESV可阻止前列腺癌细胞由G0/G1和G2期进入S期,对前列腺癌细胞增殖具有明显抑制作用,在前列腺癌治疗中具有重要价值。

Inhibition of polypeptide extract from scorpion venom (PESV) against proliferation of Prostate cancer androgen-independent cell lines in vitro

Aim To study the effects of PESV on the growth and proliferation of androgen-independent human prostate cancer line DU-145 and PC-3.Methods Cell growth inhibition rate was determined using MTT;cell cycle distribution was analysed using flow cytometry(FCM); cyclin E and p27 expression in protein level was detected using immunohistochemistry.Result PESV(dose range:40~200 mg·L -1)inhibited the growth of PC-3 in a dose-depended matter(inhibiting rate(IR)of DU-145 and PC-3 cell lines with PESV(40 mg·L -1)treatment was 30.5% and 33.1%,P<0.05,vs control,100% with 200 mg·L -1 treatment).FCM analysis showed that PESV arrested the cell cycle mainly in G_1-phase,and cells at G_0/G_1 and G_2/M phase clearly increased. Immunohistochemistry showed PESV downregulate cyclin E(grey analysis, P<0.01 vs control) and upregulated p27 expression (grey analysis, P<0.05 vs control) at protein level Conclusion PESV can inhibit PC-3 and DU-145 growth and proliferation in vitro and may play an important role in prostate cancer therapy