Inhibitory Effects Of Curcumin In Combination With Paclitaxel On Prostate Cancer Xenografted Model

Background:Prostate cancer is the most common malignancy in male.Because the chemotherapeutic drugs experience significant systemic side effects,which can severely limit the duration and dose of drug treatment that can be administered. There is increasing interest in the combined use of low doses of chemopreventive drugs with herbs.Curcumin has been proved to have pluralism biological action and nontoxic, and was shown to be a focal point of the research on prevent and therapy of tumor,including prostate cancer.Objective:To investigate the combined effects of curcumin with paclitaxel in the human prostate cancer cells PC3 xenografted tumor in nude mice, and compare the combining effects of curcumin with half dose of paclitaxel.Methods:Prostate cancer cells PC3 xenografted tumors in nude mice were used, which were randomized into four groups (n=6) and treated with vehicle (0.2 ml, ip. every 2 days for 15 times),curcumin(100 mg/kg, ip. every 2 days for 15 times), paclitaxel(10 mg/kg, ip. every 3 days for 10 times)and their combination(curcumin+half dose of paclitaxel) individually. Tumor volumes were measured every 6 days up to the 30th day. The genes expression of proliferating cell nuclear antigen (PCNA), matrix metalloproteinases (MMP)2 and inhibitor of differentiation or inhibitor of DNA binding (Id)1 of tumors was assayed by real time RT-PCR and immunohistochemistry assay respectively.Results:After 30 days treatment, curcumin and paclitaxel induced a significantly inhibition of PC3 tumor growth on the 24th and 30th day. The mean tumor volume in their combination (curcumin+half dose of paclitaxel) group was smaller than that in double dose of paclitaxel group on the 30th day (P<0.05). Curcumin or paclitaxel significantly reduced the mRNA quantities of PCNA and MMP2 in exnografts (P<0.01). In addition, curcumin induced a marked reduction of Id1mRNA quantity (P<0.01). In their combination group, the mRNA quantities of PCNA, MMP2 and Idl were obvious lower than that in paclitaxel group (P<0.05). Immunohistochemical analysis demonstrated that the protein expression of PCNA, MMP2 and Idl was also down regulated in the treated tumours.Conclusion:Curcumin combined with paclitaxel can inhibit the growth of PC3 xenografted tumors. Curcumin and paclitaxel can reduce the genes expression of PCNA and MMP2 in tumors. In addition, curcumin can reduce the gene expression of Idl in tumors. The inhibitory effects of combining curcumin with half dose of paclitaxel were better than that in paclitaxel alone treated.