Li Xiao, Jin Ningyi, Mi Zhiqiang, Lian Hai, Sun Lili, Li Xuemei, Zheng Hongling
Genetic Engineering Laboratory of PLA, The Eleventh Institute of Academy of Military Medical Sciences of PLA, Changchun, People's Republic of China.
Int J Cancer. 2006 Dec 15;119(12):2948-57. doi: 10.1002/ijc.22215.
Apoptin is a chicken anemia virus-derived, p53-independent, bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis in tumor cells. To explore the use of the Apoptin gene in cancer gene therapy, we constructed a recombinant fowlpox virus expressing the Apoptin protein (vFV-Apoptin) and compared the tumor-killing activity of the recombinant virus with that of wild-type fowlpox virus in the human hepatoma cell line HepG2. We found that although cells were somewhat resistant to the basal cytotoxic effect of wild-type fowlpox virus, infection with vFV-Apoptin caused a pronounced, additional cytotoxic effect. Furthermore, cell death and disruption of tumor integrity were apparent in the vFV-Apoptin-infected cells. We also tested whether fowlpox virus-mediated expression of Apoptin in tumor cells could stimulate an antitumor effect by injecting aggressive subcutaneous tumors derived from H22 mouse hepatoma cells in C57BL/6 mice with vFV-Apoptin. We found that fowlpox virus-mediated intratumoral expression of the Apoptin gene can induce protective and therapeutic antitumor effects and significantly increase survival. Taken together, these data indicate that infection of tumors with fowlpox virus expressing Apoptin inhibits tumor growth, induces apoptosis and may be an effective cancer treatment.
凋亡素是一种源自鸡贫血病毒的、不依赖p53且对bcl-2不敏感的凋亡蛋白，具有特异性诱导肿瘤细胞凋亡的能力。为了探索凋亡素基因在癌症基因治疗中的应用，我们构建了一种表达凋亡素蛋白的重组禽痘病毒（vFV-凋亡素），并在人肝癌细胞系HepG2中比较了该重组病毒与野生型禽痘病毒的杀瘤活性。我们发现，尽管细胞对野生型禽痘病毒的基础细胞毒性作用有一定抗性，但感染vFV-凋亡素会导致明显的额外细胞毒性作用。此外，在vFV-凋亡素感染的细胞中，细胞死亡和肿瘤完整性破坏很明显。我们还通过给C57BL/6小鼠注射源自H22小鼠肝癌细胞的侵袭性皮下肿瘤并接种vFV-凋亡素，来测试禽痘病毒介导的肿瘤细胞中凋亡素的表达是否能刺激抗肿瘤效应。我们发现，禽痘病毒介导的肿瘤内凋亡素基因表达可诱导保护性和治疗性抗肿瘤效应，并显著提高生存率。综上所述，这些数据表明，用表达凋亡素的禽痘病毒感染肿瘤可抑制肿瘤生长、诱导凋亡，可能是一种有效的癌症治疗方法。
