[Inhibitory effect of Adp53 and F56 on growth and metastasis of transplantation of the breast tumor in mice].
OBJECTIVE
To investigate the effects of Adp53 and F56 on the growth and lung metastasis of breast cancer.


METHODS
The BICR-H1 cells were inoculated into the mammary fatty pad of BALB/C nude mice and NOD/SCID mice to establish breast cancer model. Then the nude mice with xenograft tumor were randomized into group Adp53+F56, Adp53, F56 and control. The NOD/SCID mice with xenograft tumor were randomized into group Adp53+F56, Adp53, F56, Adlacz and control. They were treated for 3 weeks according to the plan, diversity of the volume and histopathology of xenograft tumor of nude mice was observed and the expressions of p53 and VEGF gene, and microvessel density (MVD) were detected by immunohistochemistry. Lung metastasis of breast cancer in NOD/SCID mice was observed.


RESULTS
(1) Intratumoral injections of Adp53, F56, and their combination resulted in an inhibition on the growth of xenograft tumor of BICR-H1 cells. The ultimate relative growth volumes of groups Adp53+F56, Adp53, F56 and control were 2.47,4.37,4.69 and 12.49 respectively. (2) After treatment, P53 positive rate of group Adp53+F56, Adp53 increased 9.4%, 6.3% than before respectively, but compared with control group, the difference is not significant (P=0.693); VEGF protein of group Adp53+F56, Adp53 and F56 decreased 21.9%, 9.4% and 3.1% than before respectively, but compared with control group, the difference was not significant (P=0.284). Necrosis and decrease of vessel in the tumor and morphological change of endothelium were observed under light microscope in the groups Adp53+F56, Adp53 and F56. MVD estimated by FVIII-RA staining of group Adp53+F56, Adp53 and F56 were 14.50+/-2.54, 16.28+/-3.44 and 18.06+/-7.66, compared with control group(24.93+/-6.53), the difference is significant (P=0.000). (3) The average number of lung metastasis of NOD/SCID mice in group Adp53+F56, Adp53 and F56 were 1.143+/-0.378, 2.750+/-0.886 and 3.375+/-0.518 respectively, lower than Adlacz group(5.000+/-0.816) and control group (5.670+/-0.817) obviously (P=0.000).


CONCLUSIONS
Adp53 combined with F56 can greatly inhibit growth and metastasis of breast cancer in vivo. The mechanism of anti-tumor effects of Adp53 and F56 may be related to the anti-angiogenesis effect on malignant tumor through inhibiting the expression and activity of VEGF.
Xiao
Shao-wen
SW
Department of Radioation Oncology, Peking University School of Oncology ,Beijing 100036, China.
Yan
Bo
B
Yang
Jing-xian
JX
Shou
Cheng-chao
CC
Zhang
Shan-wen
SW
D000260:Adenoviruses, Human / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy; D008325:Mammary Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008819:Mice, Nude; D016513:Mice, SCID; D011897:Random Allocation; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays / Q000379:methods*
D020533:Angiogenesis Inhibitors; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A