All these results indicated that overexpression of P16 might inhibit the expression of P-gp through activation of the pERK pathway. Different from this conclusion, it has been shown that the activity of ERK1/2 was enhanced in gemcitabine-resistant intrahepatic cholangiocarcinoma cells, and the use of U0126 may have a synergistic effect on tolerance to gemcitabine [21]. The gene discussed is MAPK3; the disease is intrahepatic cholangiocarcinoma.