ABSTRACT
BACKGROUND: Biocompatible gold nanoparticles (GNPs) are potentially practical and efficient agents in cancer radiotherapy applications. In this study, we demonstrated that GNPs can significantly modulate irradiation response of hepatocellular carcinoma cells in vitro and investigated the underlying mechanisms. We co-grafted galactose (GAL) targeting hepatocyte specific asialoglycoprotein receptor and Polyethylene Glycol (PEG) onto GNPs surfaces to increase GNPs targeting specificity and stability. RESULTS: This novel GAL-PEG-GNPs and bare GNPs show similar appearance and cytotoxicity profiles, while more GAL-PEG-GNPs can be effectively uptaken and could enhance cancer cell killing. CONCLUSION: GAL-PEG-GNPs have better radiosensitization to HepG2. The sensitization mechanism of GAL-PEG-GNPs is related to the apoptotic gene process activated by generation of a large amount of free radicals induced by GNPs.
Subject(s)
Asialoglycoprotein Receptor/metabolism , Carcinoma, Hepatocellular/radiotherapy , Galactose/therapeutic use , Gold/therapeutic use , Liver Neoplasms/radiotherapy , Metal Nanoparticles/therapeutic use , Polyethylene Glycols/therapeutic use , Carcinoma, Hepatocellular/metabolism , Drug Delivery Systems , Galactose/metabolism , Gold/metabolism , Hep G2 Cells , Humans , Liver Neoplasms/metabolism , Metal Nanoparticles/ultrastructure , Oxidative Stress/radiation effects , Particle Size , Polyethylene Glycols/metabolismABSTRACT
OBJECTIVE: This work aimed to investigate whether nanosilver and nanogold could modulate irradiation response of hepatocellular carcinoma cells (HepG2) in vitro and the underlying mechanisms. METHODS: Cell viability of the HCC cell lines (HepG2) was examined by the 3-(4,5-dimethylthiazol-yl)-5(3-carboxymethoxyphenyl)-2H-terazolium (MTT) assays. Clonogenic growth assays of HepG2 were determined by colony formation assays. Cell apoptosis and cell cycle distribution changes were analyzed by flow cytometry (FCM). DNA damage was assessed by monitoring γ-H2AX foci in irradiated cells with immunofluorescence microscopy. The expression of regulating molecules was analyzed by using western blotting for Bax, caspase-3, and Bcl-2, and the content of catalase (Catalase CAT), superoxide dismutase (SOD), glutathione (Total of GSH) were determined. RESULTS: Our results show that nanosilver and nanogold reduced the viability of HepG2 cells. Nanosilver and nanogold significantly enhanced the radiosensitivity of HepG2 cells. Obtained by Dq, the SER of 1/5 silver+irradiation group, 1/10 silver+irradiation group, 1/5 gold+irradiation group, 1/10 gold+irradiation group, respectively, were 1.977, 1.823, 1.762, 1.597. Immunofluorescence assays showed that there was 32.2±1.2% of irradiated HepG2. And 48.1±0.1% of 1/5 IC50 nanogold+6Gy group, 43.7±0.8% of 1/10 IC50 nanogold+6Gy group, 48.8±1.2% of 1/5 IC50 nanosilver+6Gy group,41.5±1.5% of 1/10 IC50 nanosilver+6Gy group. Nanosilver and nanogold could upregulate the expression of Bax, caspase-3 and downregulate the expression of Bcl-2. Moreover, the content of CAT, SOD and Total GSH were significantly reduced. CONCLUSION: Nanosilver and nanogold could enhance the radiationsensitivity of hepatocellular carcinoma cells. Elevated DNA damage levels and apoptosis may be responsible for this.
Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/radiotherapy , Gold/pharmacology , Metal Nanoparticles , Radiation Tolerance/drug effects , Silver/pharmacology , Antioxidants/metabolism , Apoptosis/drug effects , Apoptosis/radiation effects , Carcinoma, Hepatocellular/genetics , Caspase 3/metabolism , Cell Cycle/drug effects , Cell Cycle/radiation effects , Cell Survival/drug effects , Cell Survival/radiation effects , DNA Damage , Down-Regulation/drug effects , Down-Regulation/radiation effects , Hep G2 Cells , Humans , Metal Nanoparticles/ultrastructure , Proto-Oncogene Proteins c-bcl-2/metabolism , Radiation, Ionizing , Up-Regulation/drug effects , Up-Regulation/radiation effects , bcl-2-Associated X Protein/metabolismABSTRACT
AIM: To evaluate the value of (18)F-DG PET/CT in detecting recurrence and/or metastasis of colorectal cancer (CRC). METHODS: Combined visual analysis with semiquantitative analysis, the (18)F-DG PET/CT whole-body imaging results and the corresponding clinical data of 68 postoperative CRC patients including 48 male and 20 female with average age of 58.1 were analyzed retrospectively. RESULTS: Recurrence and/or metastasis were confirmed in 56 patients in the clinical follow-up after the PET/CT imaging. The sensitivity of PET/CT diagnosis of CRC recurrence and/or metastasis was 94.6%, and the specificity was 83.3%. The positive predictive value (PPV) was 96.4% and the negative predictive value (NPV) was 76.9%. PET/CT imaging detected one or more occult malignant lesions in 8 cases where abdominal/pelvic CT and/or ultrasonography showed negative findings, and also detected more lesions than CT or ultrasonography did in 30.4% (17/56) cases. Recurrence and/or metastasis was detected in 91.7% (22/24) cases with elevated serum CEA levels by (18)F-DG PET/CT imaging. CONCLUSION: (18)F-DG PET/CT could detect the recurrence and/or metastasis of CRC with high sensitivity and specificity.
