Coadministration of the FNIII14 Peptide Synergistically Augments the Anti-Cancer Activity of Chemotherapeutic Drugs by Activating Pro-Apoptotic Bim
| العنوان: | Coadministration of the FNIII14 Peptide Synergistically Augments the Anti-Cancer Activity of Chemotherapeutic Drugs by Activating Pro-Apoptotic Bim |
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| المؤلفون: | 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 |
| المصدر: | PLoS ONE PLoS ONE, Vol 11, Iss 9, p e0162525 (2016) |
| بيانات النشر: | Public Library of Science, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0206add475d785ac55fad8317d959a4d http://europepmc.org/articles/PMC5021278 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0206add475d785ac55fad8317d959a4d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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