• Wang Pan, Qian Wang, Yi Zhang, Naishu Zhang, Jiamin Qin, Wei Li, Jing Wang, Fangfang Wu, Lingsen Cao, and Guanglin Xu.
• Department of the College of Life Sciences, Nanjing Normal University, Nanjing, China.
• Cell. Physiol. Biochem. 2016 Jan 1; 39 (2): 481-90.

Background/AimsPaclitaxel (PTX) is one of the most effective anti-cancer drugs. However, multiple drug resistance is still the main factor that hinders the effective treatment of cancer with PTX. Several factors including YAP over-expression can cause PTX resistance. In this study, we aimed to verify the role YAP plays in PTX resistance, explore the reversal of PTX resistance by verteporfin (VP) and investigate the effect of combination therapy of PTX and VP on the PTX resistant colon cancer cells (HCT-8/T).MethodsTo study the relationship between YAP and PTX resistance, a stable YAP-over-expression or YAP silencing cell line was generated by transfected with YAP-plasmids or siYAP-RNA. WST-1 assay was performed to detect the cytotoxicity of PTX on HCT-8 and HCT-8/T cells. Clone formation assay and Transwell assay was preformed to determine the cell proliferation and invasion ability respectively. Immunofluorescence and Western blot analysis was performed for protein detection.ResultsYAP was stronger expressed in HCT-8/T than in HCT-8, and PTX resistance was positively correlated with the level of YAP expression. VP, a strongly YAP inhibitor, could reduce the PTX resistance on HCT-8/T cells without light activation by inhibiting YAP. Beside, VP and PTX combination therapy showed synergism on inhibition of YAP and cytotoxicity to HCT-8/T. Moreover, verteporfin and PTX combination therapy affect the invasion and colony formation ability and induce apoptosis of HCT-8/T cells.ConclusionsVP can reverse the PTX resistance induced by YAP over-expression in HCT-8/T cells without photoactivation through inhibiting YAP expression.© 2016 The Author(s) Published by S. Karger AG, Basel.

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