Study On Growth Interference Of Dihydroartemisinin In PC-3 Cell Lines Of Prostate Cancer In Vivo

Objective: To study the inhibitory effects of dihydroartemisinin on the growth of transplantation human prostate cancer PC-3 cells in nude mice and the expression level of Bcl-2, Bax, Survivin, VEGF and Caspase-3, and to explore the underlying action mechanism.Methods: Prostate cancer PC-3 cells were transplanted into 20 nude mice to establish the solid tumor mode. These nude mice were randomly divided into 4 groups with 5 mice in each group: control group , solvent group (dimethyl sulfoxide 1 mL/kg weight), low dose dihydroartemisinin group (DHA 100μmol/kg weight) and large dose dihydroartemisinin group (DHA 200μmol/kg weight). The tumor growth inhibition rates were calculated on day 13 after drug administration; Pathomorphism changes of PC-3 cells were observed by light microscope and transmission electron microscope after administration. Apoptosis was detected by TUNEL. The cells were stained with Hoechst 33258 and examined under fluorescence microscope to determine cell apoptosis. The positive products of Bcl-2, Bax, Survivin, VEGF and Caspase-3 were tested by immunohistochemical method. Micro-vasvulor density (MVD) was analysed by stereological method.Results: The tumor growth inhibition rates of low dose DHA group was 63.186%, and which of large dose DHA group was 69.221%. Apoptotic cells were significantly increased and TEM examination revealed that the scattered apoptotic bodies were observed in tumor tissues of DHA groups. TUNEL staining revealed that the rate of cell apoptosis rised significantly in tumor tissues of DHA groups. Fluorescence microscope examination revealed that the apoptotic cells which were stained by Hoechst 33258 were significantly increased in tumor tissues of DHA groups, and the number density of apoptotic cell significantly augmented (P < 0.05). Immunohistochemical examination revealed that the positive products of Bcl-2, Survivin and VEGF were decreased in DHA groups (P<0.05); There was no statistically significant difference between two DHA groups (P>0.05); There was no statistically significant difference between solvent group and control group too (P>0.05). Immunohistochemical examination revealed that the positive products of Bax were significantly increased in DHA groups (P< 0.05); There was no statistically significant difference between two DHA groups (P>0.05); There was no statistically significant difference between solvent group and control group too (P>0.05). Immunohistochemical examination revealed that the positive products of Caspase-3 were significantly increased in DHA groups (P< 0.05); The positive products of Caspase-3 were higher in large dose DHA group compared with low dose DHA group (P< 0.05); There was no statistically significant difference between solvent group and control group (P>0.05). MVD was significantly decreased in experimental groups (P< 0.05); The difference of MVD was not statistical significance between two experimental groups (P>0.05); The difference of MVD was not statistical significance between solvent group and experimental groups (P>0.05).Conclusion: These results demonstrated that DHA has stronger inhibitory effects on human prostate cancer cell line PC-3 cells in vivo. DHA might induce PC-3 cells to apoptosis. The action mechanism of DHA might be related with upregulating Bax and Caspase-3 and downregulating Bcl-2, Survivin and VEGF.