CONICET | Buscador de Institutos y Recursos Humanos

Colorectal cancer is the third most common cancer constituting 10% of new cancer cases in men and 11% in women. Despite the use of surgical resection and chemotherapy, nearly 50% of patients with colorectal carcinoma develop recurrent disease, highlighting the need for improved therapies. In this context curcumin (Cur), the major active ingredient of turmeric (Curcuma longa), inhibits the growth of transformed cells, has also been related with tumor regression in colon carcinogenesis in rodent models, and was found to be effective in targeting drug resistant cancer cell or cancer stem cell (CSC). This background makes this compound interesting to be combined with chemotherapeutic drugs such as oxaliplatin (Oxp) in order to improve the treatment of resistant colorectal cancer. In our laboratory, we have developed a colorectal oxaliplatin chemoresitant cell lines and oxaliplatin chemorresistant tumor generate in vivo. Thus, the aim of this work was to evaluate the effect of Cur combined with Oxp in our chemoresistant in vitro and in vivo models. We performed toxicity in-vitro assays in Oxp resistant T-84 colorectal cancer cell line developed by subculture in presence of incremental doses of Oxp. Besides we generate an in-vivo chemoresistant model by serial passaging of sensible T84 subcutaneous tumor xenografts in nude mice treated with Oxp and re-derived at least by four times. Oxp and Cur were administrated by intraperitoneal injection. We found that Cur can inhibit the proliferation in-vitro increasing the cytotoxic effect in combination with Oxp, furthermore the combination can inhibit the tumor growth in-vivo but increasing the toxic effect in healthy tissues. In conclusion we believe that the Oxp and Cur combination has a therapeutic potential but it is necessary the optimization of the drug delivery system in order to increase the dose in tumor site and decrease the dose in healthy tissues.