Variable sensitivity of endothelial cells to epirubicin in xenografts of human nasopharyngeal carcinoma CNE-2 cells.
Conventional anticancer drugs show non-specific vascular toxicity, and using anticancer drugs as angiogenesis inhibitors was suggested. However, our previous study suggested that vascular endothelial growth factor (VEGF) protected endothelial cells against chemotherapy drugs in vitro. To further test whether the vascular toxicity of anticancer drugs is active in vivo, epirubicin was i.p. injected into nude mice with s.c. xenografts of human nasopharyngeal carcinoma CNE-2 once (one-day schedule) or once a day from day 1 to day 7 (seven-day schedule). At 48 hours after the single injection or the 7th injection tumors were removed for detection of apoptosis of vascular endothelial cells vessels and the content of VEGF in tumor tissues. The results showed that epirubicin damaged tumor microvessels when the drug was given as a single dose, whereas epirubicin lost its vascular toxicity when the drug was given continuously for seven days, accompanied by higher levels of VEGF in tumor tissues. These results suggest the sensitivity of endothelial cells lining tumor vessels is variable during chemotherapy, and the protective effect of VEGF on endothelial cells might be related to the schedule of administration.
Zhang
Xiao-Shi
XS
Cancer Center; Sun Yat-Sen University; 651 Dongfeng Rood East; Guangzhou 510060 P.R. China.
Zhu
Xiao-Feng
XF
Gao
Jin-Song
JS
Ye
Yan-Li
YL
Feng
Qi-Sheng
QS
Liu
Zong-Chao
ZC
Zeng
Yi-Xin
YX
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D015251:Epirubicin / Q000633:toxicity*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008833:Microcirculation / Q000473:pathology; D009303:Nasopharyngeal Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000903:Antibiotics, Antineoplastic; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015251:Epirubicin