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      Palbociclib, a selective CDK4/6 inhibitor, restricts cell survival and epithelial‐mesenchymal transition in Panc‐1 and MiaPaCa‐2 pancreatic cancer cells

      1 , 2 , 1 , 1 , 1 , 2
      Journal of Cellular Biochemistry
      Wiley

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          Abstract

          The mortality rate of pancreatic cancer has close parallels to its incidence rate because of limited therapeutics and lack of effective prognosis. Despite various novel chemotherapeutics combinations, the 5-year survival rate is still under 5%. In the current study, we aimed to modulate the aberrantly activated PI3K/AKT pathway and epithelial-mesenchymal transition (EMT) signaling with the treatment of CDK4/6 inhibitor PD-0332991 (palbociclib) in Panc-1 and MiaPaCa-2 pancreatic cancer cells. It was found that PD-0332991 effectively reduced cell viability and proliferation dose-dependently within 24 hours. In addition, PD-0332991 induced cell cycle arrest at the G1 phase by downregulation of aberrant expression of CDK4/6 through the dephosphorylation of Rb in each cell lines. Although PD-0332991 treatment increased epithelial markers and decreased mesenchymal markers, the nuclear translocation of β-catenin was not prevented by PD-0332991 treatment, especially in MiaPaCa-2 cells. Effects of PD-0332991 on the regulation of PI3K/AKT signaling and its downstream targets such as GSK-3 were cell type-dependent. Although the activity of AKT was inhibited in both cell lines, the phosphorylation of GSK-3β at Ser9 increased only in Panc-1. In conclusion, PD-0332991 induced cell cycle arrest and reduced the cell viability of Panc-1 and MiaPaCa-2 cells. However, PD-0332991 differentially affects the regulation of the PI3K/AKT pathway and EMT process in cells due to its distinct influence on Rb and GSK-3/β-catenin signaling. Understanding the effect of PD-0332991 on the aberrantly activated signaling axis may put forward a new therapeutic strategy to reduce the cell viability and metastatic process of pancreatic cancer.

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          Journal
          Journal of Cellular Biochemistry
          J Cell Biochem
          Wiley
          0730-2312
          1097-4644
          August 12 2019
          January 2020
          July 2019
          January 2020
          : 121
          : 1
          : 508-523
          Affiliations
          [1 ]Department of Molecular Biology and Genetics, Science and Literature FacultyIstanbul Kultur UniversityIstanbul Turkey
          [2 ]Department of Genetics and Bioengineering, Faculty of EngineeringYeditepe UniversityIstanbul Turkey
          Article
          10.1002/jcb.29249
          31264276
          f32c23f6-d543-4456-8900-b748caed737e
          © 2020

          http://onlinelibrary.wiley.com/termsAndConditions#vor

          http://doi.wiley.com/10.1002/tdm_license_1.1

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