CGK733 enhances multinucleated cell formation and cytotoxicity induced by taxol in Chk1-deficient HBV-positive hepatocellular carcinoma cells

Biochemical and Biophysical Research Communications
Huan WangMingyuan Li

Abstract

Hepatocellular carcinoma (HCC) is one of the most deadly human cancers. Chronic hepatitis B virus (HBV) infection is one of the predominant risk factors associated with the development of HCC and complicates the treatment of HCC. In this study, we demonstrate that a HBV-positive HCC cell line HepG2.2.15, was more resistant to chemotherapy agents than its parental HBV-negative cell line HepG2. HBV-positive HCC cells exhibited defective Chk1 phosphorylation and increased chromosomal instability. CGK733, a small molecule inhibitor reportedly targeting the kinase activities of ATM and ATR, significantly enhanced taxol-induced cytotoxicity in HBV-positive HepG2.2.15 cells. The mechanism lies in CGK733 triggers the formation of multinucleated cells thus promotes the premature mitotic exit of taxol-induced mitotic-damaged cells through multinucleation and mitotic catastrophe in HBV-positive HepG2.2.15 cells. These results suggest that CGK733 could potentially reverse the taxol resistance in HBV-positive HCC cells and may suggest a novel strategy to treat HBV-infected HCC patients.

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Citations

May 31, 2014·BioMed Research International·Sheau-Fang YangYao-Tsung Yeh
Apr 17, 2015·Scientific Reports·Meng-Tzu WengJin-Chuan Sheu
Feb 18, 2016·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Sana FerroudjMehmet Ozturk
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Aug 8, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Betty L SlagleAleem Siddiqui
Nov 26, 2014·Viruses·Marissa M Minor, Betty L Slagle

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