首页|期刊导航|中华医学杂志（英文版）|STI571 combined with vincristine greatly suppressed the tumor formation of multidrug-resistant K562 cells in a human-nude mice xenograft model
中华医学杂志（英文版）2006，Vol.119Issue(11)：911-918,8.
STI571 combined with vincristine greatly suppressed the tumor formation of multidrug-resistant K562 cells in a human-nude mice xenograft model
STI571 combined with vincristine greatly suppressed the tumor formation of multidrug-resistant K562 cells in a human-nude mice xenograft model
摘要
Abstract
Background The development of the targeted signal transduction inhibitor STI571 has prompted us to treat chronic myeloid leukemia in different ways. Since STI571 may reverse multidrug-resistance of K562/MDR cells in vitro, we studied the effect of STI571 on multidrug-resistant K562 cells in vivo.Methods Multidrug-resistant human leukemia cell line K562-n/VCR expresses both bcr/abl fusion gene and multi-drug resistance (mdrl) gene. It is a vincristine resistant cell line subcloned from the vincristine (VCR)sensitive cell line K562-n induced by vincristine in vitro. K562-n and K562-n/VCR cells were inoculated subcutaneously into both sides of nude mice breast (5 × 106 cells/each) to establish a human leukemia xenograft model. The incidence and volume of tumor were observed. In the tumor-bearing nude mice, anti-tumor drugs vincristine, daunorubicin (DNR), STI571, and STI571 plus VCR for the treatment of mdrl and bcr/abl double positive leukemia were studied respectively.Results The tumor incidence was 100% in the nude mice inoculated with either K562-n or K562-n/VCR. The transcription of the mdrl gene and expression of P-gp were negative in K562-n cells but positive in K562-n/VCR cells. The intracellular accumulation of DNR in K562-n cells was higher than that in K562-n/VCR cells (P＜0.05).The tumor incidence of K562-n/VCR cells in nude mice was much higher than that of K562-n cells in chemotherapy groups, and the mean volume of the tumors was also larger (P＜0.05). STI571 combined with VCR significantly suppressed the proliferation of K562-n/VCR cells.Conclusions The MDR characteristics of K562-n/VCR in vivo were the same as in vitro. STI571 had a significant tumor-suppressing effect on VCR-sensitive leukemia cells and a moderate effect on MDR leukemia cells. VCR combined with STI571 had an excellent tumor-suppressing effect on both K562-n/VCR and K562-n in the human-nude mice xenograft model.关键词
K562 cells/leukemia/multidrug-resistance/imatinib mesylate/xenograft model antitumor assaysKey words
K562 cells/leukemia/multidrug-resistance/imatinib mesylate/xenograft model antitumor assays分类
医药卫生引用本文复制引用
GAO Lei,CHEN Li,FEI Xin-hong,QIU Hui-ying,ZHOU Hong,WANG Jian-min..STI571 combined with vincristine greatly suppressed the tumor formation of multidrug-resistant K562 cells in a human-nude mice xenograft model[J].中华医学杂志（英文版）,2006,119(11):911-918,8.基金项目
This work was supported in part by grants from Outstanding Physician Program of Health Bureau of Shanghai Municipal Government, Shanghai, China. （）
