Coadministration of the FNIII14 Peptide Synergistically Augments the Anti-Cancer Activity of Chemotherapeutic Drugs by Activating Pro-Apoptotic Bim

Autor: You-ichi Takizawa, Keisuke Itagaki, Toshiyuki Owaki, Shougo Akari, Ryo Hayashi, Hiroaki Kodama, Takuya Iyoda, Fumio Fukai, Hiroaki Orita, Jyunichi Taira, Yuya Tokita, Yumi Nagamine, Yoshitomi Nakane, Motomichi Fujita, Kazuki Otsuka
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Integrins
medicine.medical_treatment
Cytotoxicity
Cell
Cancer Treatment
Melanoma
Experimental
lcsh:Medicine
Apoptosis
Pharmacology
Toxicology
Pathology and Laboratory Medicine
Biochemistry
Metastasis
Mice
0302 clinical medicine
Basic Cancer Research
Medicine and Health Sciences
Medicine
Post-Translational Modification
Neoplasm Metastasis
lcsh:Science
Mammary tumor
Mice
Inbred BALB C
Multidisciplinary
Bcl-2-Like Protein 11
Pharmaceutics
Melanoma
Drug Synergism
Primary tumor
Extracellular Matrix
medicine.anatomical_structure
Oncology
030220 oncology & carcinogenesis
Female
Cellular Structures and Organelles
Signal Peptides
medicine.drug
Aclarubicin
Research Article
Drug Administration
Antineoplastic Agents
03 medical and health sciences
Drug Therapy
Cell Line
Tumor
Cell Adhesion
Animals
Humans
Doxorubicin
Chemotherapy
business.industry
lcsh:R
Biology and Life Sciences
Cancers and Neoplasms
Proteins
Mammary Neoplasms
Experimental
Cell Biology
medicine.disease
Peptide Fragments
Fibronectins
030104 developmental biology
Metastatic Tumors
Drug Resistance
Neoplasm
lcsh:Q
business
Zdroj: PLoS ONE
PLoS ONE, Vol 11, Iss 9, p e0162525 (2016)
ISSN: 1932-6203
Popis: The acquisition of drug resistance mediated by the interaction of tumor cells with the extracellular matrix (ECM), commonly referred to as cell adhesion-mediated drug resistance (CAM-DR), has been observed not only in hematopoietic tumor cells but also in solid tumor cells. We have previously demonstrated that a 22-mer peptide derived from fibronectin, FNIII14, can inhibit cell adhesion through the inactivation of β1 integrin; when coadministered with cytarabine, FNIII14 completely eradicates acute myelogenous leukemia by suppressing CAM-DR. In this study, we show that our FNIII14 peptide also enhances chemotherapy efficacy in solid tumors. Coadministration of FNIII14 synergistically enhances the cytotoxicity of doxorubicin and aclarubicin in mammary tumor and melanoma cells, respectively. The solid tumor cell chemosensitization induced by FNIII14 is dependent upon the upregulation and activation of the pro-apoptotic protein, Bim. Furthermore, the metastasis of tumor cells derived from ventrally transplanted mammary tumor grafts is suppressed by the coadministration of FNIII14 and doxorubicin. These results suggest that the coadministration of our FNIII14 peptide with chemotherapy could achieve efficient solid tumor eradication by increasing chemosensitivity and decreasing metastasis. The major causes of tumor recurrence are the existence of chemotherapy-resistant primary tumor cells and the establishment of secondary metastatic lesions. As such, coadministering FNIII14 with anti-cancer drugs could provide a promising new approach to improve the prognosis of patients with solid tumors.
Databáze: OpenAIRE
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