Caffeine Dose-dependently Potentiates the Antitumor Effect of Cisplatin on Osteosarcomas

Abstract

Background: Caffeine-assisted chemotherapy has been used in the treatment of osteosarcomas. However, there is little in vivo evidence for this treatment, and thus we sought to verify the dose and effect of caffeine in combination with cisplatin in osteosarcoma-bearing rats. Materials and Methods: Seven-week-old male Fischer rats were transplanted with chemical carcinogen-induced osteosarcoma, selected lung metastatic lesions tumor block. The osteosarcoma-bearing rats were treated with saline, caffeine, cisplatin or cisplatin and caffeine. Results: The most growth inhibition was observed in the co-administration group. When three different dosing schedules of caffeine were given, the extent of tumor inhibition was closely correlated with the average plasma concentration of caffeine. The cisplatin concentration in the tumor was significantly increased when caffeine was co-administered. Conclusion: This study confirms that a high concentration of caffeine (about 0.4 mM) is effective in enhancing the antitumor effects of cisplatin.