摘要
目的:研究SGC-7901、MKN-45、Huh-7和U87等荷瘤裸鼠模型中内皮祖细胞(endothelial progenitor cell,EPC)水平,通过检测EPC判断优福定(UFT)抗血管生成的化疗剂量。方法:建立荷瘤动物模型,UFT和环磷酰胺(CTX)对荷瘤动物模型治疗后,FCM检测外周血EPC(circulating EPC,CEP),免疫组织化学检测微血管密度(microvessel density,MVD)。结果:SGC-7901、MKN-45、Huh-7和U87等荷瘤裸鼠模型中CEP水平升高,与正常对照裸鼠相比,差异有统计学意义(P<0.05)。不同小剂量UFT持续治疗MNK-45荷瘤裸鼠,检测CEP确定UFT抗血管生成化疗时最佳生物剂量是20mg.kg-1.d-1。最大耐受剂量UFT组治疗1周时,裸鼠处于频死状态,与对照组相比,CEP明显增加(P<0.05);持续小剂量UFT组治疗3周后,与对照组相比,CEP明显降低(P<0.05)。持续小剂量UFT和CTX治疗MNK-45荷瘤裸鼠结果显示,CEP值和MVD显著相关(r=0.998,P=0.044)。结论:CEP检测可估计UFT抗血管生成化疗的最佳生物剂量和抗肿瘤疗效。
Objective： To assess endothelial progenitor cells （EPCs） in the peripheral blood of SGC-7901, MKN-45, Huh-7 and U87 xenograft in BALB/c nude mice, and to show whether circulating EPCs（CEPs） can serve as a pharmacodynamic biomarkers to determine the optimum biologic close （OBD） of metronomic UFT. Methods： The tumor-bearing animal models were established. After mice were treated with UFT and CTX, circulating EPC （CEPs） was measured by flow cytometry and microvessel density （MVD） was evaluated in parallel by immunohistochemistry. Results： We found increases in the levels of CEPs in nucle mice with SGC-7901, MKN- 45, Huh-7, and U87 xenograft compared with control group （ P 〈 0.05 ）. The nude mice with MNK-45 xenograft were treated with various low-close of UFT continuously. The OBD of UFT chemotherapy against angiogenesis was determined as 20 mg · kg^-1 · d^-1 as mea-sured by CEP detection. The nucle mice were nearly clead after treatment with UFT at maximum tolerable close for 1 week. The CEP increased significantly compared with control group （ P 〈 0.05 ）. Assessment of CEPs can determine the OBD of metronomic UFT. Maximum tolerable close and low-close metronomic chemotherapy of UFT have opposite effects on the mobilization of CEPs. The nucle mice xenografiod with MNK-45 were treated with UFT and CTX at low close continuously. We found that there was correlation between changes in CEPs and inhibition of tumor angiogenesis as measured by microvessel density （ r = 0. 998, P = 0. 044）. Conclusion ： Detec- tion of CEPs can determine the OBD and antitumor effects of metronomic chemotherapy of UFT.
出处
《肿瘤》
CAS
CSCD
北大核心
2008年第7期567-571,共5页
Tumor
关键词
肿瘤
外周血干细胞
血管生成抑制剂
剂量效应关系
药物
小鼠
裸
Neoplasms
Peripheral blood stem cell
Angiogenesis inhibitors
Dose-response relationship, drug
Mice, nude
