[Transfer of cDNAs of platelet factor 4 and N-truncated peptide inhibits solid tumor growth in vivo].
OBJECTIVE
Determine the anti-tumor angiogenic effect of PF4 and p17 - 70 using virally mediated gene transfer.


METHODS
Full-length PF4 cDNA and p17 - 70 cDNA were cloned into retroviral vector (pLXSN). KB was incubated with the supernatant of transfected PA317. PCR, RT-PCR and Western blotting analysis was used to determine the integration and expression of foreign gene. By MTT method the effects of the supernatants of PA317-PF4s and KB-PF4s on the proliferation of human umbilical vein endothelial cells (HUVEC) were studied. Tumorigenecity of KB-PF4 and KBp17 - 70 cells was assayed with xenograft tumor growth in isogenous nude mice by examining the growth rate of xenograft, survival, and histochemistry of xenograft tumor.


RESULTS
Recombinant PF4 and p17 - 70 were able to inhibit selectively HUVEC proliferation. Animal survival was significantly prolonged. Furthermore, p17 - 70 significantly prolonged animal survival compared with PF4 group (P < 0.05).


CONCLUSIONS
Transduction of p17 - 70 inhibits solid tumor growth through an anti-angiogensis mechanism. Targeted anti-angiogenesis, using retroviral-mediated PF4 gene transfer, especially p17 - 70 represents a promising strategy for cancer gene therapy.
Li
Yanhan
Y
National Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin 300020, China.
Liu
Yongjun
Y
Jin
Yixin
Y
Zhou
Yuling
Y
Cai
Yinglin
Y
Chen
Huishu
H
Zhang
Liyan
L
Han
Zhongchao
Z
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D018076:DNA, Complementary / Q000235:genetics*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007624:KB Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000517:prevention & control* / Q000628:therapy; D010446:Peptide Fragments / Q000627:therapeutic use; D010957:Plasmids / Q000235:genetics; D010978:Platelet Factor 4 / Q000235:genetics / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D018076:DNA, Complementary; D010446:Peptide Fragments; D010978:Platelet Factor 4