PD-0332991 induces G1 arrest of colorectal carcinoma cells through inhibition of the cyclin-dependent kinase-6 and retinoblastoma protein axis

Chunsheng Li, Ling Qi, Anita C. Bellail, Chunhai Hao, Tongjun Liu

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Preclinical and clinical studies have demonstrated the anticancer activity of PD-0332991, a selective cyclin-dependent kinase 4/6 (CDK4/6) inhibitor, in the treatment of various types of cancer in a retinoblastoma protein (RB)-dependent manner. However, it remains unclear whether CDK4, CDK6 or both are required for RB phosphorylation in colorectal carcinoma and thus PD-0332991 can be used to target this CDK-RB axis for the cancer therapy. The aim of this study was to determine whether CDK4, CDK6 and phosphorylated RB proteins were overexpressed in colorectal carcinoma tissues as compared to matched normal colorectal tissues. The results showed that knockdown of CDK6 but not CDK4 reduced RB phosphorylation and inhibited carcinoma cell growth. Thus, CDK6 plays a critical role in RB phosphorylation and cancer growth. PD-0332991 treatment blocked RB phosphorylation and inhibited cell growth through the induction of G1 arrest of colorectal carcinoma cells. The results demonstrated that, by targeting of CDK6-RB axis, PD-0332991 may prove to be a novel therapeutic agent in treating colorectal carcinoma.

Original languageEnglish (US)
Pages (from-to)1673-1678
Number of pages6
JournalOncology Letters
Volume7
Issue number5
DOIs
StatePublished - 2014
Externally publishedYes

Keywords

  • Cell cycle
  • Colorectal carcinoma
  • Cyclin-dependent kinase-6
  • PD-0332991
  • Retinoblastoma protein

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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