I seeds inhibit proliferation and promote apoptosis in cholangiocarcinoma cells by regulating the AGR2-mediated p38 MAPK pathway.

I seeds can effectively inhibit the growth of a variety of cancer cells. It has been used in the treatment of a variety of cancers, and has achieved certain curative effect. However, to the best of our knowledge, no report has described the effects of I seeds on the biological functions of cholangiocarcinoma (CCA) and the mechanisms underlying the effects of the seeds on this cancer. In this study, we demonstrated that I seeds could inhibit the proliferation, migration and invasion of CCA cells, as well as promoting apoptosis and blocking the cell cycle in these cells. Moreover, I seeds inhibited the growth of CCA xenografts and promoted the apoptosis of CCA cells in vivo. Furthermore, transcriptome sequencing showed that I seeds could inhibit the growth of CCA by inhibiting the expression of AGR2 and regulating p38 MAPK pathway. Finally, this finding indicated that I seeds can inhibit proliferation and promote apoptosis in CCA cells by inhibiting the expression of AGR2 and DUSP1 and increasing the expression of p-p38 MAPK and p-p53. This study provides a new research direction for studies investigating the mechanisms underlying the effects of I seeds on CCA.