Suicide effect on rat gliomas mediated by recombinant adenovirus thymidine kinase/acyclovir system

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Author:
Wang Qi()
Lu Daru()
Xing Yongna()
Xue Jinglun()
Qiu Xinfang()
Journal Title:
CHINESE MEDICAL JOURNAL
Issue:
Volume , Issue 06, 1998
DOI:
Key Word:

Abstract: Objective To establish the replicated-deficient recombinant adenovirus-mediated thymidine kinase/acyclovir (Adtk/ACV) system and to evaluate its suicide effect on rat C6 brain gliomas in vitro and in vivo.Methods The plasmid pAdtk and pJM17 were co-infected into 293 cells (adenovector packaging cells) and the results were identified by polymerase chain reaction (PCR) assay. After the glioma C6 cells were transduced by Adtk at different multiplicity of infection (MOI) and exposed to different concentrations of ACV or gancyclovir (GCV), the cell survival curves were studied, and the cell surface was observed with scanning electronic microscopy (SEM). C6 gliomas in vivo at different inoculation days were injected with Adtk intratumorally and ACV intraperitoneally daily, and the survival duration and histologic changes of the rats were observed.Results The infectious Adtk virions had a suicide effect which was enhanced with the increase in MOIs of Adtk and ACV doses along with bystander effect. Under scanning electronic microscope, special pathologic changes were observed. ACV had a similar effect as GCV but a higher dose was used. The survival duration in day 3, day 6 and day 8 groups exceeded 90 days, and the rats in day 10 group survived 28.5±4.6 days, but the survival duration in untreated C6 group and AdLacZ/ACV (adenovirus-mediated LacZ/ACV) treated group were 16.8±3.1 and 14.0±2.2 days respectively. Conclusion Adtk/ACV system can effectively kill the rat brain gliomas in vitro and in vivo.

  • [1]Eck SL, Alavi JB, Alavi A, et al. Treatment of advanced CNS malignancies with recombinant adenovirus H5.010RSVTK: a phase Ⅰ trial. Hum Gene Ther 1996; 7:1465.
  • [2]Wang Q, Lu DR, Xing YN, et al. Establishment of the recombinant adenovirus-mediated gene transfer system and expression hFIX in vivo and in vitro. J Fudan Univ 1996; 35:601.
  • [3]Bondi A, Chieregatti G, Eusebi V, et al. The use of beta-galactosidase as a tracer in immunocytochemistry. Histochemistry 1982; 76:153.
  • [4]Mosmann T. Rapid colorimetric assay for cellular growth and survival: application for proliferation and cytotoxic assays. J Immunol Methods 1983; 65:55.
  • [5]Kobayashi N, Allen N, Clendenon NR, et al. An improved rat brain-tumor model. J Neurosurg 1980; 53:808.
  • [6]Maron A, Gustin T, Le Roux A, et al. Gene therapy of rat C6 glioma using adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene: long-term follow-up by magnetic resonance imaging. Gene Ther 1996; 3:315.
  • [7]Shewach DS, Zerbe LK, Hughes TL, et al. Enhanced cytotoxicity of antiviral drugs mediated by adenovirus directed transfer of the herpes simplex virus thymidine kinase gene in rat glioma cells. Cancer Gene Ther 1994; 1:107.
  • [8]Freeman SM, Abboud CN, Whartenby KA, et al. The "bystander effect": tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res 1993; 53:5274.
  • [9]Freeman SM, Ramesh R, Abboud CN, et al. Tumor killing using the HSVtk suicide gene. Abstracts in the Fifth International Conference on Gene Therapy of Cancer. Cancer Gene Ther 1996; 3 (Suppl 6):34.
  • [10]Lu DR, Pan YJ, Zhang H, et al. Tumor therapy by HSVtk/ACV system. J Fudan Univ 1995; 34:692.
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