As the occurrence and development of HCC are often accompanied by
inflammation, the combination of
sorafenib with other therapeutic drugs, especially anti-inflammatory drugs, is one of the directions to be explored at present. Our previous research has been focused on the anti-inflammatory
drug 2,5-dimethylcelecoxib (DMC), whether DMC combined with
sorafenib could elevate the effect of inhibiting HCC deserves further exploration. In this study, we found that DMC induced
CYP3A5 expression in HCC cells in a time-dependent and concentration dependent manner. We observed that
sorafenib inhibited
CYP3A5 expression in
liver cancer cells, and activated the phosphorylation of Akt. Upregulated
CYP3A5 and DMC treatment enhanced the ability of
sorafenib to inhibit migration. The combination of DMC with
sorafenib had a synergistic effect of enhancing
drug sensitivity (CI < 1), meanwhile, inhibited the proliferation and promoted apoptosis of HCC. Activation of the AMPK pathway and inhibition of the PI3K/Akt pathway were observed in cells treated with DMC in combination with
sorafenib and could be reverted by an AMPK pathway inhibitor. Our findings suggest that DMC induces
CYP3A5 expression and enhances the anticancer effect of
sorafenib by activating AMPK, which would be a novel strategy for
drug combination to prevent drug resistance.