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Chinese Journal of Cancer Research

, Volume 15, Issue 2, pp 92–97 | Cite as

Effects ofin vivo gene transduction of anti-MDR1 ribozyme in combination with chemotherapy on multidrug-resistant human lymphoma growth in mice

  • Xu Dong-ping 
  • Wang Fu-sheng 
  • Ohnuma Takao
  • Jin Lei 
Article

Abstract

Objective: To study the effect of adenovirus- mediated transfer of anti-MDR1 ribozyme on the reversal of multidrug resistant (MDR) phenotype of P-glycoprotein (P-gp)-positive Daudi human Burkitt lymphoma bothin vitro andin vivo. Methods: A recombinant adenovirus expressing 196Rz (Adv-196Rz) was developed and functionally evaluated. SCID mice inoculated subcutaneously (s.c.) with 5×l06 Daudi/MDR20 cells were locally treated with Adv-196Rz or mock virus (Adv-Mock) at the multiplicity of infection (MOI) of 400 PFU once a day for 3 consecutive days. Then the mice were intraperitoneally (i.p.) administrated with vincristine (VCR) 450ng/g for 5 consecutive days. Results:In vitro employment of Adv-196Rz was able to interruptMDR1 transcription, to inhibit P-gp expression and to restore drug sensitivity to VCR of Daudi/MDR20 cells.In vivo, 87.5% (7/8) of Daudi/MDR20-inoculated mice treated with Adv-Mock+ VCR developed palpable tumor by the 6th week and died or were sacrificed (because of tumor weight >10% of body weight) by the 11th week. In contrast, among 9 Daudi/MDR20-inoculated mice treated with Adv-196Rz + VCR, only 3 developed tumor by the 11th, 13th and 14th week, respectively. 66.7% of mice survived >120 days in tumor-free. The survival difference between the two groups was very significant (P<0.01). Conclusion: Adenovirus-mediated Transfer of 196Rz can revert drug resistance of MDR tumor cells bothin vitro andin vivo. Adv-196Rz may prove useful as an adjuvant in the chemotherapy of P-gp mediated MDR human tumors.

Key words

MDR Ribozyme Cancer Gene therapy 

CLC number

R730.53 

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Copyright information

© Chinese Journal of Cancer Research 2003

Authors and Affiliations

  • Xu Dong-ping 
    • 1
  • Wang Fu-sheng 
    • 1
  • Ohnuma Takao
    • 2
  • Jin Lei 
    • 1
  1. 1.Department of BioengineeringThe Institute of Infectious Diseases PLABeijingChina
  2. 2.Division of Medical OncologyMount Sinai School of MedicineNew YorkUSA

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