title: Primary in vitro and in vivo evaluation of norcantharidin-chitosan/poly (vinyl alcohol) for cancer treatment.
abstract: Two novel polymer-drug conjugates norcantharidin-poly(vinyl alcohol) and norcantharidin-chitosan (NCTD-PVA and NCTD-CS) were synthesized via alcoholysis reaction and characterized by (1)H-NMR and FTIR. NCTD was released from the conjugates via hydrolysis, faster in PBS (pH 5.0) than that in PBS (pH 7.4). NCTD-PVA and NCTD-CS inhibited human esophageal carcinoma ECA-109 cell and murine breast cancer EMT6 cell growth in a dose-dependent manner. The IC50 values of NCTD, NCTD-PVA and NCTD-CS on ECA-109 cell at 48 h were 9.4 ± 0.9, 55.3 ± 3.0 and 168.8 ± 8.9 μg/ml, respectively, and the IC50 values of the three compounds on EMT6 cell were 3.1 ± 0.3, 30.5 ± 5.4 and 90.7 ± 8.1 μg/ml, respectively. The two conjugates both induced esophageal carcinoma ECA-109 cell apoptosis and arrested cell cycle at the S phase. Caspase-8 and caspase-3 were activated in the ECA-109 cell after incubating with NCTD-PVA or NCTD-CS. The primary in vivo antitumor activity was assessed in the EMT6 tumor-bearing mouse model. NCTD-PVA and NCTD-CS displayed higher tumor inhibition rates than that of free NCTD.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University , Shanghai , People's Republic of China and.
authors.forename: Mingna
authors.initials: M
authors.lastname: Li
authors.forename: Xiaofen
authors.initials: X
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Lu
authors.forename: Shengrong
authors.initials: S
authors.lastname: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D051379:Mice; D011142:Polyvinyl Alcohol / Q000008:administration & dosage* / Q000737:chemistry; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C069741:norcantharidin; D011142:Polyvinyl Alcohol; D048271:Chitosan
keywords: Antitumor drug; norcantharidin; norcantharidin-chitosan; norcantharidin-poly (vinyl alcohol); polymer–drug conjugate