Curcumin enhances anti-cancer efficacy of either gemcitabine or docetaxel on pancreatic cancer cells

Curcumin is a natural compound extracted from turmeric (Curcuma longa), which has been reported to be a promising anti-cancer drug in various human cancers. However, the effects of combination treatment of curcumin with gemcitabine or docetaxel on pancreatic cancer remains elusive. In the present study, the combinatory effects of curcumin with either gemcitabine or docetaxel on the proliferation, apoptosis, migration as well as invasion of PC cells were investigated. Calcusyn software was used to determine whether curcumin has is synergistic with gemcitabine or docetaxel. Combination index values from combinational use were all lower than 1, indicating the synergism of curcumin with gemcitabine or docetaxel on PC cells in vitro. EdU assay showed that curcumin could enhance the ability of gemcitabine or docetaxel to inhibit the proliferation of PC cells. Furthermore, the results from transmission electron microscope, DAPI staining experiments and western blot analysis revealed that curcumin may trigger apoptosis of PC cells via PARP/caspase-3 signaling pathway and reinforced pro-apoptotic ability of either gemcitabine or docetaxel. In addition, curcumin exhibited marked suppressive ability on metastasis of PC cells by wound healing and matrigel-transwell assay. Mechanistically, upregulation of TIMP1/TIMP2 with concomitant downregulation of MMP2/MMP9/N-cadherin proteins may be involved in this process. In conclusion, curcumin showed synergistic anti-cancer effects with either gemcitabine or docetaxel on PC cells.