Synergistic effect of toughening perssad-curcumin with ester and metformin on apoptosis of androgenic independent prostate cancer cell line PC-3

Abstract

Objective To study the effect of toughening genes-linking curcumin with ester and Metformin on apoptosis of androgenic independent prostate cancer cell line PC-3.Methods Immunohistochemical staining was used to detect the distribution and expression intensity of CD44 and CD133 antigens in PC-3 cells of primary and 8th passage.PC-3 cells were treated with three concentrations of Boc-phenylalanine-curcumin (BPC) combined with Metformin,BPC or Metformin alone respectively for 24 h.The growth activities of cancer cells were studied by methyl thiazol tetrazolium (MTT) colorimetry.Cell apoptosis and its rate were detected by using flowcy-tometry.The morphological changes of cancer cells were observed under electronic microscopy.Results The positive expression rate of CD44 and CD133 antigens in primary PC-3 cells was (56.5 ± 1.0) ％ and (50.7 ± 4.0) ％ respectively,which was significantly higher than that in passaged PC-3 cells [(23.1 ± 1.1)％ and (18.5 ± 2.5％) respectively].After treatment with 5 mmol/L Metformin,10-40 μmol/L BPC,5 mmol/L Metformin ± 10-40 μmol/L BPC for 24 h,the growth inhibition rate of PC-3 cells was (20.3 ± 1.7)％,(15.3 ± 1.1)％-(49.3 ±2.0)％,and (50.9 ± 1.0) ％-(68.4 ± 3.2) ％ respectively.After treatment with 5 mmol/L Metformin,40 μmol/L BPC,5 mmol/LMetformin plus 40 μmol/L BPC for 24 h,the apoptosis rate was (21.02 ± 2.10) ％,(28.04 ± 1.40) ％,and (45.03 ± 2.80) ％ respectively.There was significant difference in the growth inhibition rate and the apoptosis rate between Metformin plus BPC group and corresponding control group (P ＜0.05).After treatment with 5 mmol/L Metformin,the growth inhibition and apoptosis rate of passaged PC-3 cells was (4.95 ± 1.20)％ and (5.02 ± 1.70)％ respectively,which was significantly lower than that in primary PC-3 cells.Conclusion Metformin can enforce antiproliferative effect of BPC aganist human prostatic cancer cell line PC-3.Tumor stem cells may exist in prostate cancer PC-3 cells.Metformin possiby targetedly kills tumor stem cells which exist in prostate cancer PC-3 cells. Key words: Prostatic cancer; Metformin; Stem cell; Apoptosis