TY - JOUR T1 - Exosomal p38 Mitogen-activated Protein Kinase Promotes Tumour Repopulation in <em>TP53</em>-mutated Bile Duct Cancer Cells JF - Anticancer Research JO - Anticancer Res SP - 745 LP - 757 DO - 10.21873/anticanres.15533 VL - 42 IS - 2 AU - MAMI OSAWA AU - YASUNOBU MATSUDA AU - JUN SAKATA AU - TOSHIFUMI WAKAI Y1 - 2022/02/01 UR - http://ar.iiarjournals.org/content/42/2/745.abstract N2 - Background/Aim: Tumour repopulation is a major obstacle for successful cancer treatment. This study investigated whether anticancer agents contribute to tumour repopulation in TP53-mutated bile duct cancer cells. Materials and Methods: TP53-mutated HuCCT1 and HuH28 cells were exposed to anticancer agents, and recipient cells were exposed to their conditioned media or exosomes. The effect of inhibitors and siRNA-mediated gene silencing of p38 mitogen-activated protein kinase (MAPK) and of TP53 was analyzed by cell proliferation assays and western blotting. Results: Conditioned media from genotoxic agent-treated cells promoted proliferation of recipient cells (p&lt;0.05), and this effect was abrogated by exosome inhibitors. Exosomes from gemcitabine- or cisplatin-treated cells increased cell proliferation by 1.6- to 2.2-fold (p&lt;0.05) through p38 MAPK signalling. These effects of exosomes were inhibited by inhibition/silencing of p38 MAPK but not by TP53 silencing. Conclusion: Exosomal p38 MAPK plays a pivotal role in tumour repopulation in a TP53-independent manner. ER -