title: Cytotoxicity and therapeutic effect of irinotecan combined with selenium nanoparticles.
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.
authors: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
authors: Fuping
authors: F
authors: Gao
authors: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
authors: Qing
authors: Q
authors: Yuan
authors: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
authors: Liang
authors: L
authors: Gao
authors: Affiliated Ruikang Hospital of Guangxi University of TCM, Nanning, Guangxi 530011, China.
authors: Pengju
authors: P
authors: Cai
authors: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
authors: Huarui
authors: H
authors: Zhu
authors: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
authors: Ru
authors: R
authors: Liu
authors: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
authors: Yaling
authors: Y
authors: Wang
authors: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.
authors: Yueteng
authors: Y
authors: Wei
authors: Affiliated Ruikang Hospital of Guangxi University of TCM, Nanning, Guangxi 530011, China.
authors: Guodong
authors: G
authors: Huang
authors: Affiliated Ruikang Hospital of Guangxi University of TCM, Nanning, Guangxi 530011, China.
authors: Jian
authors: J
authors: Liang
authors: CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China. Electronic address: gaoxy@ihep.ac.cn.
authors: Xueyun
authors: X
authors: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D012643:Selenium / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D000077146:Irinotecan; D012643:Selenium; D002166:Camptothecin
keywords: Antitumor drug; Apoptosis; Nrf2-ARE pathway; Selenium nanoparticle; Toxicity