Abstract | BACKGROUND: METHODS: We explored the combination effect between a MEK1/2 inhibitor SL327 and a multi-targeted RTK inhibitor Sunitinib Malate in doxorubicin resistant ATC cells using cell viability assay, cell migration assay, nuclei morphology and caspase-3 activity analysis, as well as in vivo tumor growth assay. RESULTS: There is a significant additive effect between SL327 and Sunitinib Malate in reducing viability, increasing apoptosis, and suppressing migration of doxorubicin-resistant ATC cells. Importantly, combination of SL327 and Sunitinib Malate induced significant additive suppression of in vivo doxorubicin-resistant ATC tumor growth. CONCLUSIONS: Our results suggest that the combination of MEK1/2 inhibitor and RTK inhibitor is promising for treatment of ATC especially doxorubicin-resistant ATC. The combination might not only enhance the anti- cancer efficacy, but also reduce the side effects and overcome drug resistance developed in ATC treatment. All these might provide useful information for clinical therapeutics of ATC.
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Authors | Wei Wang, Jin Zhou, Lujie Zhao, Shulin Chen |
Journal | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
(Biomed Pharmacother)
Vol. 88
Pg. 985-990
(Apr 2017)
ISSN: 1950-6007 [Electronic] France |
PMID | 28178630
(Publication Type: Journal Article)
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Copyright | Copyright © 2017 Elsevier Masson SAS. All rights reserved. |
Chemical References |
- Antineoplastic Agents
- Indoles
- Pyrroles
- SL 327
- Taxoids
- Docetaxel
- Aminoacetonitrile
- Doxorubicin
- Caspase 3
- Sunitinib
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Topics |
- Aminoacetonitrile
(analogs & derivatives, chemistry, pharmacology, therapeutic use)
- Animals
- Antineoplastic Agents
(chemistry, pharmacology, therapeutic use)
- Antineoplastic Combined Chemotherapy Protocols
(pharmacology, therapeutic use)
- Apoptosis
(drug effects)
- Caspase 3
(metabolism)
- Cell Line, Tumor
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Cell Survival
(drug effects)
- Docetaxel
- Doxorubicin
(pharmacology, therapeutic use)
- Drug Resistance, Neoplasm
(drug effects)
- Humans
- Indoles
(chemistry, pharmacology, therapeutic use)
- Mice, Nude
- Pyrroles
(chemistry, pharmacology, therapeutic use)
- Sunitinib
- Taxoids
(pharmacology, therapeutic use)
- Thyroid Carcinoma, Anaplastic
(drug therapy, pathology)
- Thyroid Neoplasms
(drug therapy, pathology)
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