Anti-human Transferrin Receptor Monoclonal Antibodies Enhance The Anti-tumor Activity Of Curcumin In Androgen Independent Prostate Cancer Cells

Objective:To investigate the anti-tumor activity of curcumin in androgen independent prostate cancer in vitro.Methods:After PC-3 cells were treated with 6.25μmol/L,12.5μmol/L,25μmol/L, 50μmol/L, and 100μmol/L curcumin, the cell activity was determined by MTT assay. After curcumin treatment, the effects of curcumin on the proliferation of prostate cancer cells were assessed by CFSE dilution. Flow cytometery (FCM) were performed to analysis the cell cycle and the induction of apoptosis on tumor cells.Results:After treating with 50μmol/L curcumin, the proliferation index of androgen independent prostate cancer cells in vitro decreased from 7.08±0.20 to 4.38±0.19 (P< 0.05);the percentage of apoptotic cells increased from 5.34%±0.96% to 21.53%±2.87%(P< 0.05);and the percentage of G2/M phase cells increased from 34.27%±1.87% up to 57.29%±1.91%(P<0.05).Conclusion:Curcumin with the concentration of 50μmol/L and below hadn't obvious effect on cell viability of androgen independent prostate cancer cells (P<0.05). Curcumin could significantly inhibit the androgen independent prostate cancer through blocking cellular proliferation and inducing apoptosis. Objective:To investigate the effect of curcumin on the intracellular signaling pathway activities of androgen independent prostate cancer and clarify the anti-tumor mechanisms of curcunin.Methods:The PathDetect Cis-/Trans- Reporting Systems (pNF-KB-Luc, pAP-1-Luc, pElkl-Luc, pCHOP-Luc, pCREB -Luc) were transiently transfected into PC3 cells, respectively. After 8 h of transfection, cells were treated with 50μmol/L curcumin for 24 h. The activity of each signaling pathway was determined by measuring the luciferase activities of the reporter in treated and untreated transfectants.Results:Curcumin inhibited the activity of NF-κB and AP-1 associated signaling pathway significantly (P< 0.05), but had little effect on the activity of Elkl, CHOP and CREB signaling pathway.Conclusions:Curcumin exerts anti-tumor effects via inhibition of the NF-κB and AP-1 associated signaling pathway. Objective:To study the anti-tumor activity of anti-human transferrin receptor monoclonal antibody (TfR mAb) in androgen independent prostate cancer in vitro and investigate the effect of TfR mAb on the anti-tumor activity of curcumin.Methods:After curcumin treatment, transferrin receptor expression was detected by flow cytometry on androgen-independent prostate cancer cells. And the cell activity of prostate cancer cells after TfR mAb treatment was determined by MTT assay. After treating with TfR mAb and curcumin, the proliferation of prostate cancer cells were assessed by CFSE dilution. Flow cytometery (FCM) were performed to analysis the cell cycle and the induction of apoptosis on tumor cells.Results:Curcumin could increase the transferrin receptor expression of androgen-independent prostate cancer cells significantly (P<0.05). Anti-human TfR mAb alone had not significant effect on the proliferation, apoptosis and cell cycle of androgen-independent prostate cancer cells (P>0.05). But anti-human TfR mAb enhance the inhibitory effect of curcumin on the apoptosis of PC-3 cells significantly (P<0.05).Conclusion:Curcumin treatment could increase the transferrin receptor expression of androgen-independent prostate cancer cells. Anti-human TfR mAb alone had not obvious anti-tumor activity in androgen independent prostate cancer cells. Blocking the transferrin receptor could enhance the apoptosis effect of curcumin on the proliferation of androgen-independent prostate cancer cells.