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Verteporfin can Reverse the Paclitaxel Resistance Induced by YAP Over-Expression in HCT-8/T Cells without Photoactivation through Inhibiting YAP Expression. | LitMetric

AI Article Synopsis

  • - Paclitaxel (PTX) is an effective anti-cancer drug, but resistance, particularly due to over-expression of the YAP protein, complicates treatment; this study investigates YAP’s role in PTX resistance and the potential of verteporfin (VP) to reverse this resistance in colon cancer cells.
  • - Researchers created cell lines to explore how YAP affects PTX resistance, performing various assays to measure cell growth, invasion, and protein expression; findings showed that higher YAP levels in resistant cells (HCT-8/T) were linked to increased resistance to PTX.
  • - The study concluded that VP, a YAP inhibitor, successfully reversed PTX resistance in HCT-8/T cells without

Article Abstract

Background/aims: Paclitaxel (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).

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. 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.

Results: YAP 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.

Conclusions: VP can reverse the PTX resistance induced by YAP over-expression in HCT-8/T cells without photoactivation through inhibiting YAP expression.

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Source
http://dx.doi.org/10.1159/000445640DOI Listing

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