Long-Term Inhibition of Notch in A-375 Melanoma Cells Enhances Tumor Growth Through the Enhancement of AXIN1, CSNK2A3 , and CEBPA2 as Intermediate Genes in Wnt and Notch Pathways

Frontiers in Oncology
Faezeh KeyghobadiMarzieh Ebrahimi

Abstract

Notch suppression by gamma-secretase inhibitors is a valid approach against melanoma. However, most of studies have evaluated the short-term effect of DAPT on tumor cells or even cancer stem cells. In the present study, we surveyed the short-term and long-term effects of DAPT on the stem cell properties of A375 and NA8 as melanoma cell lines. The effects of DAPT were tested both in vitro and in vivo using xenograft models. In A375 with B-raf mutation, DAPT decreased the level of NOTCH1, NOTH2, and HES1 as downstream genes of the Notch pathway. This was accompanied by enhanced apoptosis after 24 h treatment, arrest in the G2-M phase, and impaired ability of colony and melanosphere formation at the short term. Moreover, tumor growth also reduced during 13 days of treatment. However, long-term treatment of DAPT promoted tumor growth in the xenograft model and enhanced the number and size of colonies and spheroids in vitro. The gene expression studies confirmed the up-regulation of Wnt and Notch downstream genes as well as AXIN1, CSNK2A3, and CEBPA2 following the removal of Notch inhibitor in vitro and in the xenograft model. Moreover, the Gompertz-based mathematical model determined a new drug resistance term in the present study....Continue Reading

References

May 19, 2005·Cancer Research·Natasha Y FrankMarkus H Frank
Oct 22, 2005·The Journal of Clinical Investigation·Klara BalintZhao-Jun Liu
Dec 16, 2006·Current Molecular Medicine·Lucio MieleBarbara Osborne
Sep 13, 2008·Cell Stem Cell·Richard Mark White, Leonard I Zon
Oct 18, 2008·The Journal of Clinical Investigation·Barbara BedogniMarianne Broome Powell
Jun 25, 2009·Cancer Research·Chelsea C PinnixMeenhard Herlyn
Sep 29, 2009·Cancer Biology & Therapy·John Panelos, Daniela Massi
Jul 6, 2010·Biochimica Et Biophysica Acta·Zhiwei WangFazlul H Sarkar
Jun 1, 2009·International Journal of Oral Science·Brian E GrottkauYun-Feng Lin
Oct 1, 2010·The Journal of Investigative Dermatology·Alberto FusiUlrich Keilholz
Mar 24, 2012·World Journal of Clinical Oncology·Murielle Mimeault, Surinder K Batra
Apr 6, 2012·Nature Reviews. Cancer·Keith T FlahertyDavid E Fisher
Apr 25, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anthony W TolcherJennifer J Wheler
May 26, 2012·Clinical and Experimental Medicine·Amalia VartanianEugenia Stepanova
Jun 1, 2011·Chinese Journal of Cancer Research = Chung-kuo Yen Cheng Yen Chiu·Li-Yu JiangJian-Hua Zheng
Aug 1, 2013·OncoTargets and Therapy·Roma Olsauskas-KuprysClodia Osipo
Oct 1, 2013·Pharmacology & Therapeutics·Naoko TakebeSherry X Yang
Apr 20, 2014·Oncotarget·Emma ShtivelmanDavid E Fisher
Jul 19, 2014·Clinical and Experimental Medicine·Daniela MurtasMaria Teresa Perra
Dec 30, 2014·PloS One·Charina E OrtegaIsabel Dominguez
Nov 19, 2015·Acta Pharmaceutica Sinica. B·Lihua Huang, Liwu Fu
Dec 18, 2015·Oncotarget·Sivapriya PonnurangamDharmalingam Subramaniam
Jul 19, 2016·Annals of Translational Medicine·José Luís ManzanoAnna Martínez-Cardús
Feb 7, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Mei-Yu HsuRhoda M Alani
May 10, 2017·Journal of Tissue Engineering and Regenerative Medicine·Leila BagheriAlessia Ongaro
Dec 6, 2017·PloS One·Melissa M J ChuaIsabel Dominguez

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Datasets Mentioned

BETA
KY769663
KY769668

Methods Mentioned

BETA
xenograft
PCR
flow cytometry

Software Mentioned

CLC Sequence Viewer
Prism
SPSS
FACSCalibur
Gene Runner
ChromasPro

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