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Cytotoxicity and therapeutic effect of irinotecan combined with selenium nanoparticles.
- Source :
-
Biomaterials [Biomaterials] 2014 Oct; Vol. 35 (31), pp. 8854-8866. Date of Electronic Publication: 2014 Jul 23. - Publication Year :
- 2014
-
Abstract
- Although chemotherapeutic drugs are widely applied for clinic tumor treatment, severe toxicity restricts their therapeutic efficacy. In this study, we reported a new form of selenium, selenium nanoparticles (Nano Se) which have significant lower toxicity and acceptable bioavailability. We investigated Nano Se as chemotherapy preventive agent to protect against toxicities of anticancer drug irinotecan and synergistically enhance the anti-tumor treatment effect in vitro and in vivo. The underlying mechanisms were also investigated. The combination of Nano Se and irinotecan showed increased cytotoxic effect with HCT-8 tumor cells likely by p53 mediated apoptosis. Nano Se inhibited growth of HCT-8 tumor cells partially through caspases mediated apoptosis. In vivo experiment showed Nano Se at a dose of 4 mg/kg/day significantly alleviated adverse effects induced by irinotecan (60 mg/kg) treatment. Nano Se alone treatment did not induce any toxic manifestations. The combination of Nano Se and irinotecan dramatically inhibited tumor growth and significantly induced apoptosis of tumor cells in HCT-8 cells xenografted tumor. Tumor inhibition rate was about 17.2%, 48.6% and 62.1% for Nano Se, irinotecan and the combination of Nano Se and irinotecan, respectively. The beneficial effects of Nano Se for tumor therapy were mainly ascribed to selectively regulating Nrf2-ARE (antioxidant responsive elements) pathway in tumor tissues and normal tissues. Our results suggest Nano Se is a promising selenium species with potential application in cancer treatment.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents administration & dosage
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Apoptosis drug effects
Camptothecin administration & dosage
Camptothecin therapeutic use
Cell Line, Tumor
Female
Humans
Irinotecan
Mice, Inbred BALB C
Mice, Nude
Nanoparticles administration & dosage
Neoplasms metabolism
Neoplasms pathology
Rats
Selenium administration & dosage
Antineoplastic Agents therapeutic use
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Camptothecin analogs & derivatives
Nanoparticles therapeutic use
Neoplasms drug therapy
Selenium therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1878-5905
- Volume :
- 35
- Issue :
- 31
- Database :
- MEDLINE
- Journal :
- Biomaterials
- Publication Type :
- Academic Journal
- Accession number :
- 25064805
- Full Text :
- https://doi.org/10.1016/j.biomaterials.2014.07.004