Experimetal Study On Growth Inhibitory Of Human Cervical Cancer Line HeLa And On Inhibition Of Growth And VEGF Expression Of Human Cervical Cancer Xenografts In Nude Mice By 6, 8-ditrifluoromethyl-7-acetoxychrysin, A Novel Chrysin Derivative

Objective To compare the inhibition effect of chrysin and 6,8-ditrifluoromethyl-7-acetoxychrysin(dFMAChR), a novel chrysin derivative, on proliferation in cervical cancer cell lines HeLa in vitro and to explore the inhibitiory effect of growth and VEGF expression of xenograft of human cervical cancer by dFMAChR in vivo.Methods The growth inhibitory effects of human cervical cancer line HeLa by treatment dFMAChR and ChR with various concentrations from 0.3 to 30μM for 72h were determined using MTT assay ,by cisplatin and taxol as positive control medicine.We established human cervical carcinoma xenograft in nude mouse model and the anti-cervical cancer effect of dFMAChR in vivo was evaluated. Expression of PCNA and VEGF in human cervical cancer xenografts were detected by SP immunohistochemistry.Results MTT assays in vitro showed dFMAChR and ChR inhibited significantly the proliferation of HeLa cells in a concentration-dependent manner from 0.3 to 30μM concentrations. The IC50 value of dFMAChR to HeLa cells was 5.87μM,while the IC50 value of ChR was 30.74μM, which indicated the inhibition effect of the former was superior to the latter(P﹤0.05).After treatment with dFMAChR in nude mice model, the tumor weight inhibition rate of dFMAChR in 20mg/kg,40mg/kg,80mg/kg concentration was 42.3%,64.0% and 71.3% respectively,which was statictically significant compared with control group treated with NS( P<0.05).The WBC , LDH, GPT, GOT,BUN,and SCr in nude mouse of dFMAChR group was not statictically significant compared with control group treated with NS(P﹥0.05).Analysis of expression of VEGF and PCNA protein by SP immunohistochemistry showed that they can be down-regulated by dFMAChR at higher concentration.Conclusions The present study suggests that dFMAChR and ChR can inhibit the proliferation of human cervical cancer line HeLa cells cultured in vitro and the effect of dFMAChR on human cervical cancer line HeLa cells line was stronger than its lead cpmpound, ChR. dFMAChR can inhibit significantly the tumor growth of human cervical cancer line HeLa cells in nude mice,there is an accordant dose-respose relationship accordant at 20-80mg/kg concertration level, and possesses low toxicities to lude mouse. DFMAChR show a negative effect on the angiogenesis in tumor xenograft of human cervical cancer by dFMAChR ,as a result, which down-regulating the expression of PCNA and VEGF.