The Effect And Its Mechanism Of Oridonin On Androgen Independent Prostate Cancer Xenografts In Nude Mice

PartⅠ:In vivo Suppression of androgen independent prostate cancer growth by oridoninObjective:To evaluated efficacy oforidonin against DU145 xenografts growth.Methods:DU145 cells were injected subcutaneously to 20 male BALB/c-nude mice and those mice were randomly divided into two groups:control, oridonin 15mg/kg/d.On the day after the incubation mice were fed the 0.9%saline solution or odidonin every day for 7 weeks.Those mice were observed and tumor sizes were measured every week with vernier calipers.The volume calculated by the formula:length×width×height×π/6.At the end of experiments,two growth curves were obtained.Results:The average volume of tumors of two groups after 7 weeks were 163.69±58.73 mm~3(control group) and 68.55±29.37 mm~3(oridonin group ) (P=0.0328).The growth of DU145 tumor in "oridonin" group were significantly inhibited and the inhibition ratio was 58.12%.Conclusion:Oridonin can inhibit the growth of androgen independent prostate cancer in vivo.PartⅡ:The study of molecular mechanism of oridonin on androgen independent prostate cancerObjective:To learn the effects of oridonin on G1/S regulatory factors,apoptosis related genes,immune escape related gene and some other factors like IL-6,NF-kB in androgen independent prostate cancer xenografts.To elucidate several molecular regulations of oridonin on AIPCa cells.To explore the multiple molecular mechanism of growth arrest by oridonin.Methods:The tumor tissue was kut down from each mouse when partⅠwas over.Three samples of each group were chosen randomly for research.The mRNA expression of P16 and P21(G1/S regulatory factors),Bax and Bcl-2(apoptosis related genes),IDO(immune escape related gene),IL-6 and NF-kB were measured by PCR.The differece between two groups was analyzed.Results:The average relative concentration after using oridonin.P16:from 0.46 (control) to 0.95(oridonin)(P＜0.05);P21:from 0.12(control) to 0.48(oridonin) (P＞0.05);Bax:from 0.24(control) to 0.38(oridonin)(P＜0.05);Bcl-2:from 0.13 (control) to 0.45(oridonin)(P＜0.05);IL-6:from 0.33(control) to 0.02(oridonin) (P＜0.05);NF-kB:from 0.73(control) to 0.19(oridonin)(P＞0.05);IDO:from 0.08 (control) to 0.00(oridonin)(P＜0.01).The expressions of P16,Bax,Bcl-2 were elevated and the expressions of IDO,IL-6 were decreased in oridonin group(p＜0.05).However, the change of P21 and NF-kB were no difference statistically.Conclusion:Negative regulation on cell cycle,decreasing secretion,inhibiting immune escape maybe the molecular mechanism of oridonin.