Li Yanhan, Liu Yongjun, Jin Yixin, Zhou Yuling, Cai Yinglin, Chen Huishu, Zhang Liyan, Han Zhongchao
National Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin 300020, China.
Zhonghua Yi Xue Za Zhi. 2002 Jan 10;82(1):35-8.
Determine the anti-tumor angiogenic effect of PF4 and p17 - 70 using virally mediated gene transfer.
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.
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).
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.
利用病毒介导的基因转移确定PF4和p17 - 70的抗肿瘤血管生成作用。
将全长PF4 cDNA和p17 - 70 cDNA克隆到逆转录病毒载体（pLXSN）中。用转染的PA317的上清液孵育KB。采用PCR、RT-PCR和蛋白质印迹分析来确定外源基因的整合和表达。通过MTT法研究PA317 - PF4s和KB - PF4s的上清液对人脐静脉内皮细胞（HUVEC）增殖的影响。通过检测异种移植瘤的生长速率、生存期和异种移植瘤的组织化学，用同源裸鼠体内异种移植瘤生长来测定KB - PF4和KBp17 - 70细胞的致瘤性。
重组PF4和p17 - 70能够选择性抑制HUVEC增殖。动物生存期显著延长。此外，与PF4组相比，p17 - 70显著延长了动物生存期（P < 0.05）。
p17 - 70的转导通过抗血管生成机制抑制实体瘤生长。利用逆转录病毒介导的PF4基因转移，尤其是p17 - 70进行靶向抗血管生成是一种有前景的癌症基因治疗策略。
