[Effect of rapamycin and chloroquine on osteosarcoma].

Objective: To investigate the combination effect of anti-tumor agent rapamycin and anti-autophagy agent chloroquine on osteosarcoma. Methods: The inhibition effect of rapamycin or chloroquine and combination of both on human osteosarcoma cell line 143B measured with CCK-8 box.The combination index at different concentration was calculated, and the synergism effect range was analysed.The effect of combined therapy on cell cycle and apoptosis via flow cytometric was analyzted.Setting up murine subcutaneous xenograft model, the combination effect of antitumor in vivo observed. Results: Either of them, rapamycin or chloroquine had an antitumor effect in vitro (RAPA: IC50=1.5 nmol/L; CQ: IC50=400 μmol/L). When the inhibition rate 40%<fa<70%, the combination had synergism effect (CI<1) at different concentration.Moreover, when CQ at 200 μmol/L, the synergism effect was the most obvious, CI(min)=0.255.The flow cytometric analysis display rapamycin at 1.5 nmol/L had slightly promote apoptosis effect (16.1%±4.4%), and had distinct cell cycle arrest, mainly blocked at G0/G1 phase (73.5%±10.6%; control group: 46.7%±7.7%; P <0.001). While combined with chloroquine, the apoptosis cell obviously increased (21.3%±6.8%; P <0.05). The xenograft model also confirmed that rapamycin combined with chloroquine had a better antitumor effect than single usage (relative tumor proliferation rate; T/C%.CQ: 98.4%±11.6%; RAPA: 65.5%±7.5%; CQ+ RAPA: 42.0%±3.4%). Conclusion: Rapamycin combine with chloroquine can increase the antitumor efficacy, and the combination therapy maybe a potential therapeutic regimen.