Targeting Foxm1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum-Resistant Ovarian Cancer

International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society
Gina L WesthoffNelson N H Teng

Abstract

Aberrantly activated FOXM1 (forkhead box protein M1) leading to uncontrolled cell proliferation and dysregulation of FOXM1 transcription network occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if targeting the FOXM1 pathway with thiostrepton could improve the efficacy of paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo. Human ovarian cancer cell lines and patients' ascites cells were treated with paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and cytotoxicity was assessed. Drug combination effects were determined by calculating the combination index values using the Chou and Talalay method. Quantitative real-time polymerase chain reaction was performed to determine changes in FOXM1 expression and its downstream targets. Ovarian cancer cell lines and the patients' ascites cancer cells had an overexpression of FOXM1 expression levels. Targeting FOXM1 with thiostrepton decreased FOXM1 mRNA expression and its downstream targets such as CCNB1, CDC25B, leading to cell death in both cell lines and patients' ascites cancer cells. Furthermore, addition of thiostrepton to paclitaxel and cisp...Continue Reading

References

Feb 4, 2005·Nature Cell Biology·Robert H Costa
Feb 22, 2005·Neoplasia : an International Journal for Oncology Research·Christian PilarskyRobert Grützmann
May 16, 2008·Expert Opinion on Therapeutic Targets·Andrei L Gartel
Jun 5, 2010·The Journal of Biological Chemistry·Christopher T WalshAlbert A Bowers
Jun 10, 2010·Cancer Research·Janai R CarrPradip Raychaudhuri
Jun 30, 2011·Cancer Research·Pradip Raychaudhuri, Hyun Jung Park
Jul 2, 2011·Nature·UNKNOWN Cancer Genome Atlas Research Network
Aug 24, 2011·Nature Chemistry·Nagaratna S HegdeShankar Balasubramanian
Oct 8, 2011·Biochimica Et Biophysica Acta·Chuay-Yeng KooEric W-F Lam
Oct 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Tom WalshElizabeth M Swisher
Dec 3, 2011·Cell Cycle·Andrei L Gartel
Oct 5, 2012·Methods in Enzymology·Feifei Zhang, Wendy L Kelly
Sep 24, 2014·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Vilius RudaitisRamunas Janavicius
Oct 29, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Qian ZhongWei-Ting Hwang
Nov 13, 2014·Nature Communications·Michael V GormallyShankar Balasubramanian
Jul 15, 2015·Bioorganic & Medicinal Chemistry·Yi ChenNelson N H Teng
Sep 26, 2015·Cellular Signalling·Gabriela Nestal de MoraesRaquel C Maia

❮ Previous
Next ❯

Citations

Jan 11, 2020·International Journal of Oncology·Hualei BuBeihua Kong
Apr 18, 2019·Investigational New Drugs·Yen-Bin HsuMing-Ying Lan
Nov 23, 2020·Journal of Cancer Research and Clinical Oncology·Yuichi ShibuiYoshinao Oda
May 2, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Pei CaiBo Ouyang

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.