Chemokine CCL20 Promotes the Paclitaxel Resistance of CD44CD117 Cells Via the Notch1 Signaling Pathway in Ovarian Cancer

Studies have found that C‑C motif chemokine ligand 20 (CCL20)/C‑C motif chemokine receptor 6 (CCR6)/notch receptor 1 (Notch1) signaling serves an important role in various diseases, but its role and mechanism in ovarian cancer remains to be elucidated. The aim of the present study was to investigate the underlying mechanism of CCL20/CCR6/Notch1 signaling in paclitaxel (PTX) resistance of a CD44CD117 subgroup of cells in ovarian cancer. The CD44CD117 cells were isolated from SKOV3 cells, followed by determination of the PTX resistance and the CCR6/Notch1 axis. Notch1 was silenced in the CD44CD117 subgroup and these cells were treated with CCL20, followed by examination of PTX resistance and the CCR6/Notch1 axis. Furthermore, in nude mice, CD44CD117 and CD44CD117 cells were used to establish the xenograft model and cells were treated with PTX and/or CCL20, followed by proliferation, apoptosis, reactive oxygen species (ROS) and mechanism analyses. Higher expression levels of Oct4, CCR6, Notch1 and ATP binding cassette subfamily G member 1 (ABCG1), increased sphere formation ability, IC and proliferative ability, as well as lower ROS levels and apoptosis were observed in CD44CD117 cells compared with the CD44CD117 cells. It was found that CCL20 could significantly increase the expression levels of Oct4, CCR6, Notch1 and ABCG1, enhance the IC, sphere formation ability and proliferation, as well as decrease the ROS and apoptosis levels in the CD44CD117 cells. However, Notch1 knockdown could markedly reverse these changes. Moreover, CCL20 could significantly increase the proliferation and expression levels of Oct4, CCR6, Notch1 and ABCG1 in the CD44CD117 groups compared with the CD44CD117 groups. After treatment with PTX, apoptosis and ROS levels were decreased in the CD44CD117 groups compared with the CD44CD117 groups. Collectively, the present results demonstrated that, via the Notch1 pathway, CCL20/CCR6 may promote the stemness and PTX resistance of CD44CD117 cells in ovarian cancer.