姜黄素和紫杉醇联用对前列腺癌PC3裸鼠移植瘤作用的研究(英文)

Inhibitory Effects of Curcumin in Combination with Paclitaxel on Prostate Cancer Xenografted Model

目的:探讨姜黄素和半量紫杉醇联用对前列腺癌PC3裸鼠移植瘤生长增殖的影响及其机制。方法:构建人雄激素非依赖性前列腺癌细胞系PC3裸小鼠皮下移植瘤模型,随机分为溶酶对照组,姜黄素组,紫杉醇组和姜黄素+紫杉醇(半量)组(n=6)。姜黄素每隔2天腹腔注射100mg/kg,紫杉醇每3天腹腔注射10mg/kg,联合组紫杉醇减半,对照组注射药物溶剂。每6天测量计算移植瘤体积并绘制肿瘤生长曲线。药物注射30天后,取移植瘤组织标本分别进行免疫组化和定量RT-PCR,检测金属基质蛋白酶2(MMP2),增殖细胞核抗原(PCNA)蛋白及mRNA的表达。结果:移植瘤体积在24～30天时,姜黄素组和紫杉醇组肿瘤体积较对照组有不同程度的减小。姜黄素+紫杉醇(半量)组在第30天内肿瘤生长体积和紫杉醇组相近,30天后合用组肿瘤体积小于单纯紫杉醇组(P<0.05)。姜黄素和紫杉醇明显降低PC3移植瘤组织中PCNA和MMP2mRNA的表达(P<0.01)。姜黄素+紫杉醇(半量)组瘤组织中PCNA和MMP2的mRNA表达均低于紫杉醇组(P<0.05)。免疫组化染色显示PCNA和MMP2蛋白表达在治疗组均降低,和瘤组织中mRNA表达变化相一致。结论姜黄素可减少化疗药物的用量,从而在一定程度上可以减轻化疗药物的毒副作用。

Objective： To investigate the combined effects of curcumin with half doses of paclitaxel in the human prostate cancer cells PC3 xenografted tumor in nude mice. Methods： Prostate cancer cells PC3 xenografted tumors in nude mice were used, which were randomized into four groups and treated with vehicle, curcumin, paclitaxel and their combination （curcumin＋half dose of paclitaxel） individually. Tumor volumes were measured every 6 days up to the 30^th day. The genes expression of proliferating cell nuclear antigen （PCNA） and matrix metalloproteinases （MMP）2 of tumors was assayed by real time RT-PCR and immunohistochemistry assay respectively. Results： Curcumin and paclitaxel induced a significantly inhibition of PC3 tumor growth on the 24^th and 30th day. The mean tumor volume in their combination group was smaller than that in double dose ofpaclitaxel group on the 30^th day （P〈0.05）. Curcumin or paclitaxel significantly reduced the quantities of PCNA and MMP2 mRNA （P〈0.01）. In their combination group, the mRNA quantities of PCNA and MMP2 were obvious lower compared with paclitaxel group （P〈0.05）. Immunohistochemical analysis demonstrated that the protein expression of PCNA or MMP2 was also down regulated in the treated tumours. Conclusions： Combined curcumin with paclitaxel may be an effective therapy for hormone-refractory prostate cancer （HRPC）. The dose ofpaclitaxel in their combination can be reduced, and thus the side effects ofpaclitaxel should also be decreased.