The Antitumor Pharmacodynamics Study Of The Polyethylene Glycol-irinotecan

Objective:Polyethylene glycol-irinotecan(YP-Pegol)is an irinotecan derivative,the irinotecan molecule was contained by polyethylene glycol(PEG)molecules through the covalent bond with the PEG molecule to form conjugated polymers to obtain long term and less toxicity.The aim of this study was to evaluate the inhibitory effect of YP-Pegol on the growth of transplanted tumor of human breast cancer xenograft model(MCF-7/ADR)in nude mice.Methods: 1,The drug resistance index of MCF-7/ADR cells was evaluated by MTT assay before the start of the experiment;2,The inhibitory effect of YP-Pegol on the proliferation of MCF-7/ADR cells was evaluated by MTT assay;3,MCF-7/ADR cells were injected into the nude mice to establish the human breast cancer xenograft model in the nude mice,to evaluating the inhibitory effect of YP-Pegol on the human breast cancer xenograft model in the nude mice;4,The effect of YP-Pegol on MCF-7/ADR cell cycle were detected by flow cytometry.Results: 1,The resistance index of MCF-7/ADR cell was 8.2 and the IC50 of adriamycin on MCF-7/ADR cells was 14.16 ?g·m L-1;2,The IC50 of YP-Pegol on MCF-7/ADR cell was 44.2 ?g·mL-1 and the IC50 of YP-Pegol on MCF-7 cell was 27.7?g·mL-1;3,The data were analyzed by SPSS 19.0,compared with the negative control group,YP-Pegol 20 mg·kg-1 dose group,YP-Pegol 60 mg·kg-1 dose group,irinotecan group(60 mg·kg-1)and the positive control group(gemcitabine group,60 mg·kg-1)had no significant difference in body weight;Compared with the negative control group,the tumor volume of each treatment group including the YP-Pegol 20 mg·kg-1 dose group,YP-Pegol 60 mg·kg-1 dose group,irinotecan group(60 mg·kg-1)and positive control group(gemcitabine group,60 mg·kg-1)tumor volume was less than the negative control group(vehicle control group)(P <0.05,P <0.01);Compared with the negative control group,The relative tumor volume(RTV)of YP-Pegol low dose group,YP-Pegol high dose group,irinotecan injection group and positive control group was lower than the negative control group(P <0.05,P <0.01);The relative tumor proliferation rate(T/C,%)of the positive control group,irinotecan hydrochloride injection group and YP-Pegol high dose group were 38.7,19.9 and 25.3(<40%).4,After treatment with YP-Pegol,the cell cycle distribution of MCF-7 and MCF-7/ADR cells has changed,and the proportion of cells in S phase increased.Conclusion: YP-Pegol had no significant inhibitory effect on MCF-7 cells and MCF-7/ ADR cells in vitro.YP-Pegol high dose group(60 mg·kg-1)has a significant inhibitory effect on the human breast cancer xenograft model of the MCF-7/ADR cells in nude mice;YP-Pegol exerts anti-tumor effect by blocking the DNA replication in cell.