Suppression of tumorigenicity in cervical carcinoma HeLa cells by an episomal form of adeno-associated virus.
To compare the oncosuppressive activity of integrated and episomal adeno-associated virus (AAV), two Epstein-Barr virus (EBV) derived episomal form vectors, p205 and p220, were used to generate plasmids containing episomal AAV. HeLa cells transfected with p205, p220, and the plasmids with forward (pA205-1, pA220-1) and reverse (pA205-1, pA220-2) orientation of inserted AAV DNA were designated H205, H220, HA205-1, HA220-1, HA205-1, and Ha220-2, respectively. The respective average copy numbers of pA205 and pA220 per cell are 4.9-6.9 and 4.3. The AAV-transfected HeLa cells displayed growth inhibition when compared to parental and the vector-transfected HeLa cells. Nude mice assay showed that the tumor size from HA205-1 and HA205-2 cells were 11.3 and 22.6%, and those from HA220-1 and HA220-2 cells were 54.8 and 57.3%, respectively, when compared to parental HeLa cells. HA205-1 cells containing forward AAV insert exerted more oncosuppressive effect than HA205-2 cells containing reverse AAV insert. Our data indicate that the episomal AAV can exert oncosuppressive activity as compared to the integrated AAV in HeLa cells.
Wu
F Y
FY
Division of Cancer Research, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, R.O.C.
Wu
C Y
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Lin
C H
CH
Wu
C H
CH
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000517:prevention & control / Q000821:virology*; D002472:Cell Transformation, Viral; D003673:Defective Viruses / Q000502:physiology*; D000229:Dependovirus / Q000502:physiology*; D005260:Female; D005822:Genetic Vectors / Q000502:physiology*; D006367:HeLa Cells / Q000473:pathology / Q000821:virology*; D006378:Helper Viruses / Q000502:physiology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology; D014162:Transfection; D014412:Tumor Virus Infections / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*; D014775:Virus Activation; D016662:Virus Integration; D017735:Virus Latency