[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).

CONCLUSION

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.