Effects of TNP-470 on proliferation and apoptosis in human colon cancer xenografts in nude mice.
OBJECTIVE
To study the effect of TNP-470 on cell growth, proliferation and apoptosis in human colon cancer xenografts in nude mice.


METHODS
Human colon cancer xenografts were transplanted into 20 nude mice. Mice were randomly divided into two groups. TNP-470 treated group received TNP-470(30 mg/kg, s.c) every other day and the control group received a sham injection of same volume saline solution. They were sacrificed after 4 weeks and their tumors were processed for histological examination. The expression of proliferating cell nuclear antigen (PCNA) in tumors was detected using immunohistochemical method with image analysis, and apoptosis in tumor cells was measured by TdT-mediated biotinyated-dUTP nick end labeling (TUNEL) staining.


RESULTS
Comparing with controls, tumor growth was significantly inhibited in TNP-470 treated group, the inhibitory rate being 54.4 %. Expression of PCNA in tumors of TNP-470 treated group (PI 54.32+/-11.47) was significantly lower than that of control group (PI 88.54+/-12.36), P<0.01. Apoptosis index (AI) of TNP-470 treated group (18.95+/-1.71) was significantly higher than that of control group (7.26+/-1.44), P<0.001, typical morphological change of apoptosis in tumor cells was observed in TNP-470 treated group.


CONCLUSIONS
Besides the anti-angiogenic effects, TNP-470 can inhibit tumor growth by inhibiting the proliferation and inducing apoptosis of tumor cells.
Huang
Zong-Hai
ZH
Department of Surgery, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, Guangdong Province, China. hghigh@gdvnet.com
Fan
Ying-Fang
YF
Xia
Hu
H
Feng
Hao-Miao
HM
Tang
Fu-Xiang
FX
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D003510:Cyclohexanes; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012717:Sesquiterpenes / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol