Study on chemopreventive and on gemcitabine-based chemoresistance effects of flavonoid containing mixture in pancreatic adenocarcinoma cell lin

The 5-year survival rate of patients with pancreatic ductal adenocarcinoma (PDAC), which constitutes 85-95% of pancreatic cancers, is 9%. Though agents containing more than one chemotherapeutics are used in the therapy of locally advanced or metastatic tumors of patients who have high performance score, Gemcitabine monotherapy is still golden standart in the therapy of patients who are not eligible for surgical operation and combination chemotherapy. In Panc-1 cells and Gemcitabine-resistant Panc-1 cells (Panc-1/GEM) which were established by gradually increasing concentrations of GEM, the cytotoxicity and anti-migrative effects of a phenolic mixture containing flavonoids and combination of GEM and the mixture were calculated via CCK-8 assay and wound-healing assay, respectively. Additionally, the expressions of NDRG1 and MRP5 genes were evaluated by RT-PCR. It is found that the cytotoxic effects of the mixture in both cell lines are not significantly different. Furthermore, Gemcitabine and the mixture have moderate synergistics effects in Panc-1/GEM cells. The mixture has anti-migration effects in both cell lines. Importantly, in Panc-1/GEM cells, the levels of mRNAs of NDRG1 and MRP5 genes are lower than the levels of Panc-1 cells. In Panc-1 cells, GEM and the mixture does not change the levels of two genes. Both increase the levels of NDRG1, but only the mixture elevates the levels of MRP5 in resistant-cells. In conclusion, the mixture could prevent migration of pancreas cancer cells and increases NDRG1 levels in only resistant-cells and further researches are needed to elucidate potential anti-cancer, anti-proliferative and anti-migrative effects on locally advanced and GEM-resistant PDAC tumors.