Combined therapy of p53-wt and drug in an orthotopic multidrug-resistant human lung cancer model

Abstract

Balb/c nu/nu mice were inoculated intratracheally with multidrug-resistant human lung cancer cells GLK containing p53 mutation at codon 245 and treated with intratracheal instillation of p53-wt retroviral vector (pDOR53W) to increase cell chemosensitivity, and then with intraperitoneal injection of doxorubicin. 30 d after tumor cell inoculation, 75% of the control mice showed macroscopic tumors in the lung. Sole pDOR53W suppressed GLK tumor formation in 68% of mice; sole doxorubicin 33.3%, but the combination of pDOR53W and doxorubicin 88.9 %. The exogenous p53 sequence was detected and confirmed in the tumor that grew after treatment with pDOR53W retroviral vector by PCR and Southern blot hybridization with p53 cDNA. These results suggested that direct administration of a retroviral vector expressing p53-wt combined with treatment of anticancer agent was an effective therapeutic method for multidrug-resistant human lung cancer.