Antitumor effects of a recombinant fowlpox virus expressing Apoptin in vivo and in vitro.
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.
Li
Xiao
X
Genetic Engineering Laboratory of PLA, The Eleventh Institute of Academy of Military Medical Sciences of PLA, Changchun, People's Republic of China.
Jin
Ningyi
N
Mi
Zhiqiang
Z
Lian
Hai
H
Sun
Lili
L
Li
Xuemei
X
Zheng
Hongling
H
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D036022:Capsid Proteins / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000235:genetics / Q000502:physiology; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D005260:Female; D005587:Fowlpox virus / Q000235:genetics*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012074:Remission Induction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
D036022:Capsid Proteins; D011993:Recombinant Fusion Proteins; C091717:VP3 protein, Chicken anemia virus