Studies On Molecular Mechanisms Of Verteporfin Could Reverse The Paclitaxel Resistance In HCT-8/T Cells Without Photoactivation Through Inhibiting YAP Expression

Paclitaxel(PTX) is one of the most effective anti-cancer drugs of all.However,multiple drug resistance is still the main factor that hinder the effective treatments of PTX for cancer.Several factors can cause PTX resistance and YAP over-expressing is one kind of these.Objective:In this study,we aimed to verify the character that YAP played during the occurrence of PTX resistance,explore the reversal of PTX resistance of verteporfin and investigated the effect of combination therapy of PTX and verteporfin on the PTX resistant colon cancer cells(HCT-8/T).Methods:To 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.Clony formation assay and Transwell assay was preformed to determine the cell proliferation and invasion ability respectively.Immunofluorescence method and Western blot analysis was performed for protein detection.Result:we indicated that YAP was higher expressed in HCT-8/T than in HCT-8,and PTX resistance was positively correlated with the level of YAP expression.Verteporfin,a strongly YAP inhibitor,could reduce the PTX resistance on HCT-8/T cells without light activation by inhibiting YAP.Beside,verteporfin and PTX combination therapy showed synergism on inhibition of YAP and cytotoxicity to HCT-8/T.Moreover,verteporfin and PTX combination therapy could affect the invasion and colony formation ability and induce apoptosis on HCT-8/T cells.In conclusion,Verteporfin can reverse the PTX resistance induced by YAP over-expression in HCT-8/T cells without photoactivation through inhibiting YAP expression.