Enhanced antitumor effect of lower-dose and longer-term CPT-11 treatment in combination with low-dose celecoxib against neuroblastoma xenografts

Background We have previously reported that the combination of low-dose (5.9 mg/kg/dose) irinotecan (CPT-11) and simultaneous low-dose (5 mg/kg/dose) celecoxib, a cyclooxygenase-2 inhibitor, administered for 20 consecutive days, had synergistic antitumor activity against human neuroblastoma xenografts in mice. Possible further antitumor efficacy of lower-dose and longer-term CPT-11 combined with simultaneous low-dose celecoxib was investigated for chemosensitive TNB9 and multi-drug resistant TS-N-2 nu neuroblastoma xenografts. Methods The time from initiation of drug treatment to tumor regrowth, tumor doubling time, and body weight change of mice were evaluated between treatments with lower-dose (3 mg/kg/dose) CPT-11 alone and the combination of the two drugs for 60 consecutive days. Induction of apoptosis and autophagy during treatments were analyzed by immunoblotting, real-time quantitative RT-PCR, TUNEL assay, and immunohistochemistry. Results The combination of the two drugs administered for 60 consecutive days resulted in a significantly longer time to tumor regrowth ( p