Aquaporin5 (AQP5), a water channel protein, has been reported to possess the oncogenic potential in multiple types of malignancies, including colorectal cancer (CRC). However, its effect on the chemosensitivity of CRC cells remains elusive.Hence, the present study aimed to investigate the effect of AQP5 silencing in CRC cells on 5-fluorouracil (5-FU) sensitivity and elucidate the underlying mechanisms. A short hairpin RNA (shRNA) construct targeting AQP5 was transfected into HCT116 or HT29 cells to generate stably AQP5-silenced cell lines. The effects of AQP5 knockdown on cell viability, apoptosis, tumor growth and 5-FU chemoresistance were evaluated. Relative protein levels of Wn... More
Aquaporin5 (AQP5), a water channel protein, has been reported to possess the oncogenic potential in multiple types of malignancies, including colorectal cancer (CRC). However, its effect on the chemosensitivity of CRC cells remains elusive.Hence, the present study aimed to investigate the effect of AQP5 silencing in CRC cells on 5-fluorouracil (5-FU) sensitivity and elucidate the underlying mechanisms. A short hairpin RNA (shRNA) construct targeting AQP5 was transfected into HCT116 or HT29 cells to generate stably AQP5-silenced cell lines. The effects of AQP5 knockdown on cell viability, apoptosis, tumor growth and 5-FU chemoresistance were evaluated. Relative protein levels of Wnt/β-catenin pathway effectors were also measured. The results showed that silencing of AQP5 increased the chemosensitivity of CRC cells to 5-FU, facilitated 5-FU -mediated cell apoptosis, suppressed tumor growth, and 5-FU chemoresistance in vivo. Furthermore, the effect of AQP5 on 5-FU chemosensitivity was mediated by the Wnt/β-catenin pathway. Silencing of AQP5 inhibited the Wnt/β-catenin signaling. Whereas, overexpression of the degradation-resistant mutant of β-catenin (S33Y) reversed cell apoptosis induced by AQP5 silencing. Taken together, these results suggest that AQP5 silencing enhances the sensitivity of CRC cells to 5FU, and the underlying mechanism is related to inhibition of the Wnt/β-catenin pathway. AQP5 could be a useful therapeutic agent for CRC treatment.
