Activated Notch signaling is required for hepatitis B virus X protein to promote proliferation and survival of human hepatic cells

Cancer Letters
Fan WangBin Cheng

Abstract

Hepatitis B virus X protein (HBx) is a multifunctional oncoprotein which plays a crucial role in the pathogenesis of hepatocellular carcinoma (HCC). However, the exact mechanisms remain controversial. Here we show that HBx strongly stimulated cell growth, promoted cell cycle progression and inhibited apoptosis of human non-tumor hepatic cell line L02 cells. It also accelerated tumor formation of L02 cells in BALB/c nude mice. Furthermore, Notch signaling components were upregulated in HBx-expressing L02 cells compared to normal L02 cells. However, blocking Notch signaling with a γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) attenuated cell growth, shortened the S phase of cell cycle and promoted apoptosis of HBx-expressing L02 cell in a dose- and time-dependent manner, but normal L02 cells were not significantly affected by Notch signaling blocking. Therefore, our findings demonstrate that HBx could promote the growth of human non-tumor hepatic cell line L02 cells both in vitro and in vivo, which may require the activation of Notch signaling pathway.

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Citations

Aug 2, 2011·Acta Pharmacologica Sinica·Guang-yao KongXiao-dong Zhang
Dec 15, 2012·Clinical and Translational Gastroenterology·Nirupama TrehanpatiShiv Kumar Sarin
Aug 8, 2014·Breast Cancer : the Journal of the Japanese Breast Cancer Society·Yaojian RaoJiawei Cui
Jun 19, 2012·Annual Review of Genomics and Human Genetics·Ze-Guang Han
Feb 25, 2015·Journal of Cellular Physiology·Millore X M LuoWilliam K K Wu
Oct 4, 2015·Cancer Letters·Waihong ChungJack R Wands
Mar 7, 2013·The Journal of Surgical Research·Changjiang HuGuangping Liang
Jul 12, 2016·Biomarkers in Cancer·Ranjit Chauhan, Nivedita Lahiri
Jun 30, 2018·Reviews in Medical Virology·Elenaé Vázquez-UlloaAdriana Contreras-Paredes
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Jul 16, 2014·International Journal of Oncology·Qian SunBin Cheng
Sep 4, 2020·World Journal of Clinical Oncology·Ariel Ka-Man ChowLui Ng
Jun 15, 2021·Frontiers in Cardiovascular Medicine·Randa M Breikaa, Brenda Lilly

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