论文部分内容阅读
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 both in vitro and in vivo. Methods: A recombinant adenovirus expressing 196Rz (Adv-196Rz) was developed and functionally evaluated. SCID mice inoculated subcutaneously (s.c.) with 5×106 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 interrupt MDR1 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