ANTIANGIOGENETIC THERAPY WITH PLATELET FACTOR-4 TO LIVER CANCER.

【目的】血小板因子4（Platelet Factor 4，PF4）通过抑制血管内皮细胞的生长，抑制新生血管的形成，从而显著抑制肿瘤的生长。在本研究中，将编码PF4释放的腺病毒载体直接注射到实验性肝肿瘤中，以确定是否可以抑制肿瘤生长。【材料与方法】构建PF4释放腺病毒载体，以人脐静脉内皮细胞（HUVEC）为实验材料，观察其对血管内皮细胞生长的抑制作用。接下来，将编码PF 4释放的腺病毒载体在体内抑制培养的人肝癌细胞（HepG）和HUVEC的新血管形成的能力与对照载体的能力进行比较。[结果] PF4对实验性肝癌的生长有明显的抑制作用，而生理盐水（对照）对抑制作用无明显影响。腺病毒载体编码PF4释放没有显着抑制人脐静脉内皮细胞（HUVEC）在体外的生长。此外，将编码PF 4释放的腺病毒载体在体内抑制培养的人肝癌细胞（HepG）和HUVEC的新血管形成的能力与对照载体的能力进行比较，但没有证实显著的抑制。在本研究中未能检测到显著差异可归因于腺病毒载体的稳定性和再现性。

[Objective] Platelet Factor 4 (PF4) has been shown to inhibit neovascularization by suppressing the growth of vascular endothelial cells, and thus significantly suppressing tumor growth. In the present study, an adenovirus vector encoding PF4 release was directly injected into experimental liver tumors to determine whether tumor growth could be suppressed.[Materials and Methods] An adenovirus vector encoding PF4 release was made, and we determined whether the vector could suppress growth of vascular endothelial cells in vitro using human umbilical vein endothelial cells (HUVEC). Next, the ability of the adenovirus vector encoding PF4 release to inhibit neovascularization of cultured human hepatoma cells (HepG) and HUVEC in vivo was compared to that of a control vector.[Results] PF4 was found to suppress the growth of experimental liver tumors, while physiological saline (control) did not affect suppression significantly. Adenovirus vector encoding PF4 release did not significantly suppress growth of human umbilical vein endothelial cells (HUVEC) in vitro. Further, the ability of the adenovirus vector encoding PF4 release to inhibit the neovascularization of cultured human hepatoma cells (HepG) and HUVEC in vivo was compared to that of a control vector, but no significant suppression was confirmed. Failure to detect significant differences in the present study was attributable to the stability and reproducibility of the adenovirus vector.