ANTIANGIOGENETIC THERAPY WITH PLATELET FACTOR-4 TO LIVER CANCER.

[目的]研究表明，血小板第4因子(PF4)通过抑制血管内皮细胞的生长而抑制血管新生，从而显著抑制肿瘤生长。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癌中，以确定是否可以抑制肿瘤的生长。[材料与方法]制备编码PF4释放的腺病毒载体，并用人脐静脉内皮细胞(HUVEC)检测该载体是否能在体外抑制血管内皮细胞的生长。接着，比较了携带PF4释放基因的腺病毒载体对体外培养的人肝癌细胞(HepG)和人脐静脉内皮细胞(HUVEC)血管生成的抑制作用。[结果]PF4能抑制实验性肝肿瘤的生长，而生理盐水(对照组)对抑制作用不明显。携带PF4释放基因的腺病毒载体对人脐静脉内皮细胞(HUVEC)的生长无明显抑制作用。此外，比较了携带PF4释放基因的腺病毒载体对体内培养的人肝癌细胞(HepG)和人脐静脉内皮细胞(HUVEC)新生血管的抑制作用，但没有明显的抑制作用。未能检测到本研究中的显著差异是由于腺病毒载体的稳定性和重复性。

[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.