Synergism effect of 131 I-Herceptin and high-energy X-ray on HER2 overexpressed breast cancer cells / 中国生化药物杂志

ABSTRACT

Objective To study the synergism effect of 131 I-Herceptin and high-energy X-ray on HER2 overexpressed breast cancer SK-BR-3 cells.Methods The protein expression and gene amplification of human epidermal growth factor receptor-2 ( HER2 ) in SK-BR-3 cells were identified by immunohistochemistry and fluorescence in situ hybridization ( FISH ) method, 131 I-Herceptin was prepared by iodogen method, and the IC15 concentration of 131 I-Herceptin on SK-BR-3 cell were selected by MTT method.The cells were divided into control group and drug group according to 131 I-Herceptin used or not, and were delivered five different doses of external irradiation (0,2,4 and 6Gy), and the synergism effect was detected by colonogenic assay.The cells were divided into blank group, drug group(131I-Herceptin), X-ray group(2 Gy external irradiation) and combination group (131I-Herceptin+2 Gy external irradiation), the apoptosis rate and death rate were detected by AO/EB method and cell cycle were detected by flow cytometry.Results The labling rate, radiochemical purity and specific radioactivity of 131 I-Herceptin were 86.8%, 93.9% and 868.3 μci/mg, respectively.The IC15 of 131 I-Herceptin was 15.625μci/mL.131 I-Herceptin and high-energy X-ray significantly reduced surviving fraction ( SF) ( F=628.888,F=964.97,P<0.05) and there were interactions between them (F=113.046,P<0.05).There were significant differences in apoptosis rate and death rate among blank group, drug group, X-ray group and combination group(F=103.324,F=13.33,all P<0.05),and there were significant differences of pairwise comparison (P<0.05).After irradiation and 131I-Herceptin administration, the cell cycle changed obviously from G1-phase to G2-and S-phase.Conclusion 131 I-Herceptin combined with high-energy X-ray has the synergism effect on HER2 overexpressed breast cancer SK-BR-3 cells.