TUBB3 Reverses Resistance to Docetaxel and Cabazitaxel in Prostate Cancer.

Antineoplastic Agents / pharmacology Cell Line, Tumor Chromones / pharmacology Docetaxel / pharmacology Drug Resistance, Neoplasm / drug effects Enzyme Inhibitors / pharmacology Gene Knockdown Techniques Humans Male Morpholines / pharmacology PTEN Phosphohydrolase / metabolism Prostatic Neoplasms / drug therapy Protein Binding Taxoids / pharmacology Tubulin / genetics
LY294002 PTEN TUBB3 cabazitaxel cross-resistance docetaxel prostate cancer

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
13 Aug 2019
Historique:
received: 22 07 2019
revised: 03 08 2019
accepted: 05 08 2019
entrez: 16 8 2019
pubmed: 16 8 2019
medline: 17 1 2020
Statut: epublish

Résumé

Recent studies have reported that TUBB3 overexpression is involved in docetaxel (DTX) resistance in prostate cancer (PCa). The aim of this study was to clarify the role of TUBB3 in DTX and cabazitaxel (CBZ) resistance, and cross-resistance between DTX and CBZ in PCa. We analyzed the effect of TUBB3 knockdown on DTX and CBZ resistance and examined the interaction between TUBB3 and PTEN. We also investigated the role of phosphoinositide 3-kinases (PI3K) inhibitor (LY294002) in DTX and CBZ resistance. TUBB3 expression was upregulated in DTX-resistant and CBZ-resistant cells. TUBB3 knockdown re-sensitized DTX-resistant cells to DTX and CBZ-resistant cells to CBZ. Additionally, TUBB3 knockdown re-sensitized DTX-resistant cell lines to CBZ, indicating that TUBB3 mediates cross-resistance between DTX and CBZ. Knockdown of TUBB3 enhanced PTEN expression, and PTEN knockout enhanced TUBB3 expression. LY294002 suppressed TUBB3 expression in DTX-resistant and CBZ-resistant cell lines. LY294002 re-sensitized DTX-resistant cell lines to DTX and CBZ-resistant cell lines to CBZ. These results suggest that TUBB3 is involved in DTX resistance and CBZ resistance. A combination of LY294002/DTX and that of LY294002/CBZ could be potential strategies for PCa treatment.

Identifiants

DOI: 10.3390/ijms20163936 PMID: 31412591 PMC: PMC6719236
pubmed: 31412591
pii: ijms20163936
doi: 10.3390/ijms20163936
pmc: PMC6719236
pii:
doi:

Substances chimiques

Antineoplastic Agents 0
Chromones 0
Enzyme Inhibitors 0
Morpholines 0
TUBB3 protein, human 0
Taxoids 0
Tubulin 0
Docetaxel 15H5577CQD
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one 31M2U1DVID
cabazitaxel 51F690397J
PTEN Phosphohydrolase EC 3.1.3.67

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Grants-in-Aid for Scientific Research
ID : 19K18586

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Auteurs

Yohei Sekino (Y)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan. akikosekino@gmail.com.

Xiangrui Han (X)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

Takafumi Kawaguchi (T)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

Takashi Babasaki (T)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

Keisuke Goto (K)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

Shogo Inoue (S)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

Tetsutaro Hayashi (T)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

Jun Teishima (J)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

Masaki Shiota (M)

Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
ORCID: 0000-0002-3306-4858

Wataru Yasui (W)

Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

Akio Matsubara (A)

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

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Classifications MeSH

Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Benzopyranes › 4H-1-Benzopyran-4-ones › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Composés chimiques organiques › Hydrocarbures › Terpènes › Diterpènes › Taxoïdes › Docetaxel › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance aux médicaments antinéoplasiques › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Techniques d'investigation › Techniques génétiques › Ciblage de gène › Techniques de knock-down de gènes › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Composés hétérocycliques › Composés hétéromonocycliques › Oxazines › Morpholines › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Phosphohydrolase PTEN › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Maladies urogénitales › Tumeurs de l'appareil urogénital › Tumeurs de l'appareil génital mâle › Tumeurs de la prostate › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Métabolisme › Liaison aux protéines › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Composés chimiques organiques › Hydrocarbures › Terpènes › Diterpènes › Taxoïdes › TUBB3 Reverses Resistance to Docetaxel and...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Tubuline › TUBB3 Reverses Resistance to Docetaxel and...