Radiosensitizing Effect Of Berberine On Prostate Cancer LNCaP Cells In Hypoxia In Vivo And Vitro

Objective To investigate the radiosensitization of berberine onLNCaP cells in hypoxia and its mechanism in vivo and vitro. Methods1. Thecytotoxicity and radiosensitization of berberine were investigated by using MTT、clongenic assay and the apoptosis rate of Cell flow method on LNCaP cells in vitro, andthe expression of HIF-1α and VEGF protein were evaluated by western blot andimmumofluorescence methods.2. LNCaP cells were inoculated into the nude mice toestablish tumor model. Mice were randomly divided into4groups: control group,berberine group, radiation group and berberine+radiation group when average volumeof tumor were about125mm3. During the term of treatment, the volume of tumors weremeasured every2days. After36days treatment, mice were killed and tumor tissueswere harvested for Western Blot to detect HIF-1α and VEGF. Results1. Cell growthwas inhibited by berberine in a dose-dependent manner and the IC50of berberine was220.36μM. Clonogenic assay showed that berberine could markedly enhance thehypoxic LNCaP cells radiosensitivity and the sensitizing enhancement ratio(SER) of30μM、50μM berberine were1.40、1.77, respectively. After24h treated withberberine(0,30,50μM) on LNCaP cells in hypoxia，6Gy dose was given the cells.3hlater, the apoptosis rate of the cells treated with berberine inereased obiviously than thecells without berberine, meanwhile, the apoptosis rate of50μM berberine inereasedobiviously than the30μM berberine. Moreover, the protein expression of HIF-1α andVEGF on LNCaP cells in hypoxia were significantly inhibited due to the treatment ofberberine by WB and immumofluorescence.2. The growth of tumor was significantlyinhibited by berberine combined with radiation and its inhibition rate was74.3％invitro. The expression level of HIF-1α and VEGF was obviously decreased in theberberine plus radiation compared with other groups by WB. Conclusions Berberinehas radiosensitizing effect on LNCaP cells in hypoxia in vivo and vitro, which might berelated to inhibit the HIF-1α and VEGF expression.