Bergamottin potentializes the cytotoxic activity of gemcitabine through inhibition of mdr1 on pancreatic cancer cell line aspc-1

Sarah Hassan., Jean Peluso., Guy Fuhrmann and Genevieve Ubeaud-Sequier

Pancreatic cancer is one of the most aggressive cancers, with only about 5% of patients surviving 5 years past the initial diagnosis. Gemcitabine monotherapy is the standard of treatment for patients with metastatic pancreatic cancer. Here, we examined the efficacy of combined treatments of bergamottin and gemcitabine in human pancreatic cancer AsPC-1 cells. For that purpose, the pro- apoptotic effects of gemcitabine were studied in presence or absence of bergamottin, in order to evaluate if this latter is able to potentialize gemcitabine cytotoxicity. Our study aims to investigate the implication of MDR1 in resistance to gemcitabine and if bergamottin could target these drug efflux pumps in AsPC-1 cells by flow cytometric. We observed that 5 μg/ml gemcitabine in combination with 15 μg/ml bergamottin was more effective than gemcitabine alone as shown by increasing in the percentage of dead cells up to 60%. In addition, the combination of gemcitabine and bergamottin increased the expression levels of cleaved caspase-3 and p53. Moreover our results demonstrated that bergamottin inhibits the efflux activity of MDR1. In conclusion, our study in vitro suggests therefore that chemotherapy with gemcitabine might be significantly increased upon combination with bergamottin and then may be promising agents for novel combination therapy.

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