An oleanolic acid derivative, K73‐03, inhibits pancreatic cancer cells proliferation in vitro and in vivo via blocking EGFR/Akt pathway

Abstract Oleanolic acid (OA) and its derivatives show potent anticancer function. Pancreatic cancer (PC) is the fourth core motive of cancer‐related deaths worldwide. Epidermal growth factor receptor (EGFR) has been implicated in PC and has been validated as a therapeutic target. Our study demonstrated that K73‐03, an OA derivative, was identified as a potent inhibitor of EGFR by using reverse pharmacophore screening and molecular dynamics simulation assays. Moreover, Western blot analysis showed that K73‐03 markedly suppressed the levels of phosphorylated‐EGFR (p‐EGFR) and phosphorylated‐Akt (p‐Akt). The inhibitory effect of K73‐03 on PC cells was assessed in vitro and in vivo. Mechanistically, K73‐03 effectively inhibited the cell proliferation of PC cells, and induced apoptosis and autophagy of ASPC‐1 cells in a dose‐dependent manner. Additionally, pretreatment with chloroquine, an autophagy inhibitor, significantly inhibited K73‐03‐induced autophagy and enhanced K73‐03‐induced apoptotic cell death. K73‐03 also strongly repressed ASPC‐1 cells xenograft growth in vivo. Thus, all these findings provided new clues about OA analog K73‐03 as an effective anticancer agent targeted EGFR against ASPC‐1 cells, it is worth further evaluation in the future.