Paclitaxel-Induced Src Activation Is Inhibited by Dasatinib Treatment, Independently of Cancer Stem Cell Properties, in a Mouse Model of Ovarian Cancer

Cancers
Elif KadifeNuzhat Ahmed

Abstract

Approximately seventy percent of ovarian cancer patients succumb to the disease within the first 5 years of diagnosis, even after successful surgery and effective chemotherapy treatment. A small subset of chemotherapy resistant cancer stem cells (CSCs) cause relapse of ovarian cancers. This study investigated the association between paclitaxel-mediated Src activation (p-Src) and CSC populations in driving ovarian cancer progression. We demonstrate that patients with high-stage serous ovarian carcinomas have significantly elevated levels of p-Src, compared to patient with low-stage and benign ovarian tumours. Additionally, p-Src was significantly enhanced in ascites-derived tumour cells obtained from recurrent patients, compared to chemonaïve patients. Paclitaxel treatment increased Src activation in ovarian cancer cells, causing enrichment of CSC marker expression in the surviving cells in vitro and in xenografts of nude mice. Dasatinib in combination with paclitaxel significantly suppressed p-Src in ovarian cancer cell lines and xenografts but had no effect on the expression of CSC markers. However, combination of paclitaxel and Dasatinib showed lower trend in invasion in liver and pancreas, compared to paclitaxel-only treatme...Continue Reading

References

Dec 15, 2000·Oncogene·R B Irby, T J Yeatman
Apr 21, 2005·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·R F Ozols
Jan 29, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Michael BraveRichard Pazdur
Apr 15, 2009·Journal of Surgical Oncology·Jalid SehouliOskay-Ozcelik Gülten
Oct 1, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·George D DemetriT R Jeffry Evans
Oct 29, 2009·British Journal of Cancer·G E KonecnyD J Slamon
Mar 17, 2010·Cancer Treatment Reviews·John Araujo, Christopher Logothetis
Apr 27, 2010·Nature Cell Biology·Louis VermeulenJan Paul Medema
Jan 7, 2011·Gynecologic Oncology·Deanna TeohAngeles Alvarez Secord
Feb 8, 2011·CA: a Cancer Journal for Clinicians·Ahmedin JemalDavid Forman
Jan 25, 2012·Nature Reviews. Cancer·Nicola McCarthy
Jan 27, 2012·Stem Cell Reviews and Reports·Cristóbal Aguilar-GallardoCarlos Simón
Aug 14, 2012·Journal of Cellular Biochemistry·Nuzhat AhmedMichael Quinn
Aug 23, 2012·Annals of Oncology : Official Journal of the European Society for Medical Oncology·L C HankerUNKNOWN AGO and GINECO study group
Jan 2, 2013·Molecular and Cellular Biochemistry·Yong-Wen HuangXiao-Feng Zhu
Feb 1, 2013·International Journal of Cancer. Journal International Du Cancer·James W HodgeSofia R Gameiro
Mar 27, 2013·International Journal of Molecular Sciences·Mi Jeong Kwon, Young Kee Shin
Jul 3, 2013·Molecular Aspects of Medicine·Nuzhat AhmedJock K Findlay
May 14, 2014·International Journal of Oncology·Xiaosi HanL Burt Nabors
Apr 11, 2015·Cancer Cell·Brian Ruffell, Lisa M Coussens
May 16, 2015·Molecular Medicine Reports·Juan XiaoJundong Li
Aug 2, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Paola MazziGiorgio Berton
Aug 26, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Daniel Elias, Henrik J Ditzel
Oct 22, 2016·Clinical and Translational Science·I NakachiR S Stearman
Aug 22, 2017·International Journal of Molecular Sciences·Shosuke KawanishiMariko Murata

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Citations

Sep 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yi ZhangFan-Hao Meng
Aug 14, 2021·European Journal of Medicinal Chemistry·Ya-Xi YeHai-Liang Zhu

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Methods Mentioned

BETA
hysterectomy
nuclear translocation
flow cytometry
xenografts
Protein Assay
Electrophoresis

Software Mentioned

CellR
DeltaPixView
Excel
Aperio
GraphPad Prism
ImageJ
SoftMax® Pro
Cell Quest TM

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