Effects of TNP-470 on proliferation and apoptosis in human colon cancer xenografts in nude mice

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AIM: To study the effect of TNP-470 on cell growth,proliferation and apoptosis in human colon cancer xenograftsin nude mice.METHODS: Human colon cancer xenografts weretransplanted into 20 nude mice. Mice were randomly dividedinto two groups. TNP-470 treated group received TNP-470(30 mg/kg, s.c) every other day and the control groupreceived a sham injection of same volume saline solution.They were sacrificed after 4 weeks and their tumors wereprocessed for histological examination. The expression ofproliferating cell nuclear antigen (PCNA) in tumors wasdetected using immunohistochemical method with imageanalysis, and apoptosis in tumor cells was measured by TdT-mediated biotinyated-dUTP nick end labeling (TUNEL)staining.RESULTS: Comparing with controls, tumor growth wassignificantly inhibited in TNP-470 treated group, the inhibitoryrate being 54.4 %. Expression of PCNA in tumors of TNP-470 treated group (PI 54.32±11.47) was significantly lowerthan 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 tumorcells was observed in TNP-470 treated group.CONCLUSION: Besides the anti-angiogenic effects, TNP-470 can inhibit tumor growth by inhibiting the proliferationand inducing apoptosis of tumor cells.
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