[Effect of nobiletin on K562 cells xenograft in nude mice].
OBJECTIVE
To observe the inhibitory effect of citrus extract nobiletin on K562 cells xenograft in nude mice and discuss its anticancer activity and mechanism.


METHODS
The model of K562 cells xenograft was established in nude mice. Twenty-five nude mice were divided to five groups. After 24 hrs of inoculation with K562 tumor cells subcutaneously, 1% CMC-Na in the nude mice of model control group, nobiletin (12.5, 25, 50 mg x kg(-1)) in the nude mice of nobiletin groups and CTX (20 mg x kg(-1)) in positive control group were administered once every day. The nude mice were killed at 18th day-point of administration. The inhibitory rate of nobiletin on tumor was calculated according to the measured tumor weight. Immunohistochemistry assay was used to determine the effect of nobiletin on VEGF expression and MVD, and CAM assay was used to detect the effect of nobiletin on vessel regeneration.


RESULTS
Nobiletin have notable inhibition on K562 cells xenograft in nude mice comparing with model control group (P < 0.01), the inhibitory rate of nobiletin groups were 36% -58%. The results of immunohistochemical technology showed that the expression of VEGF in nobiletin groups decreased significantly comparing with the model control group (P < 0.05, P < 0.01, P < 0.01). Nobiletin could remarkably decrease the angiogenesis within tumor tissues. The expression of CD34 in nobiletin low dose group and high dose group was lower than that in model control group (P < 0.05, P < 0.01). The result of CAM indicated that 4 microg and 2 microg nobiletin could inhibit the new blood vessels of CAM (P < 0.01).


CONCLUSIONS
Nobiletin inhibited the tumor growth and angiogenesis by reducing the VEGF expression of K562 cells xenograft in nude mice.
Wang
Yuwei
Y
Department of Pharmacology, Institute of Medicine and Pharmacy, Yangzhou University, Yangzhou 225001, China. wyw1981@163.com
Su
Mengqi
M
Yin
Jiale
J
Zhang
Hongquan
H
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002957:Citrus / Q000737:chemistry*; D004195:Disease Models, Animal; D047309:Flavones / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020014:K562 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D047309:Flavones; D042442:Vascular Endothelial Growth Factors; C008661:nobiletin