title: Aquaporin 3 facilitates chemoresistance in gastric cancer cells to cisplatinviaautophagy.
abstract: Cisplatin (cDDP) remains one of the first-line chemotherapeutic agents for gastric cancer (GC) treatment, and resistance to cDDP is the major limitation in its clinical application. Mechanisms of cDDP resistance have been shown to be varied and complicated. Aquaporin 3 (AQP3) has been demonstrated to be overexpressed in GC tissues and is thought to be involved in GC carcinogenesis and progression. However, the role of AQP3 in chemosensitivity of GC to cytotoxic agents remains unknown. In this study, we show that AQP3 overexpression induced resistance to cDDP in AGS cells (P<0.05), and AQP3 knockdown increased the chemosensitivity in MGC803 and SGC7901 cells (P<0.05). Moreover, cDDP treatment enhanced AQP3 expression in MGC803, SGC7901 and AGS cells. AQP3 overexpression promoted the conversion of LC3-I to LC3-II in AGS cells, whereas AQP3 knockdown inhibited this conversion in MGC803 and SGC7901 cells. AQP3 upregulation increased Atg5 and Beclin-1 expression, and inhibited P62 expression in AGS cells, whereas AQP3 knockdown showed the opposite results in MGC803 and SGC7901 cells. Chloroquine (CQ), an autophagy inhibitor, enhanced the cytotoxicity of cDDP in GC cells, and CQ reversed the chemoresistance to cDDP caused by AQP3 overexpression in GC cells. Together, our data demonstrate that AQP3 facilitates cisplatin resistance in gastric cancer cellsviaautophagy, and suggest that the development of AQP3-based tumor therapeutics could play a key role in future GC treatment strategies.
authors.affiliation: Division of Gastrointestinal Surgery, Department of General Surgery, First Affiliated Hospital, Nanjing Medical University , Nanjing 210029, China.
authors.forename: Xuqiang
authors.initials: X
authors.lastname: Dong
authors.affiliation: Division of Gastrointestinal Surgery, Department of General Surgery, First Affiliated Hospital, Nanjing Medical University , Nanjing 210029, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Sir Run Run Hospital, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Yangchun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Division of Gastrointestinal Surgery, Department of General Surgery, First Affiliated Hospital, Nanjing Medical University , Nanjing 210029, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Wen
authors.affiliation: School of Public Health, Nanjing Medical University , Nanjing 211166, China.
authors.forename: Shoulin
authors.initials: S
authors.lastname: Wang
authors.affiliation: Division of Gastrointestinal Surgery, Department of General Surgery, First Affiliated Hospital, Nanjing Medical University , Nanjing 210029, China.
authors.forename: Lizong
authors.initials: L
authors.lastname: Shen