ABSTRACT
Photodynamic therapy (PDT) is a promising cancer treatment modality that uses dye-sensitized photooxidation of biologic matter in target tissue. This study explored effects of the photosensitizer BCPD-17 during PDT for osteosarcoma. LM-8 osteosarcoma cells were treated with BCPD-17 and cell viability after laser irradiation was assessed in vitro with the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The effects of BCPD-17 during PDT recurrence were then examined on tumor-bearing mice in vivo. BCPD-17 had dose- dependent cytotoxic effects on LM-8 osteosarcoma cells after laser irradiation which also had energy-dependent effects on the cells. The rate of local recurrence was reduced when marginal resection of mice tumors was followed by BCPD-17-mediated PDT. Our results indicated BCPD-17-mediated PDT in combination with marginal resection of tumors is a potentially new effective treatment for osteosarcoma.
Subject(s)
Neoplasm Recurrence, Local/drug therapy , Osteosarcoma/drug therapy , Photochemotherapy , Photosensitizing Agents/pharmacology , Porphyrins/pharmacology , Animals , Apoptosis/drug effects , Bone Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Female , Mice , Mice, Inbred C3H , Mice, Nude , Neoplasm Recurrence, Local/prevention & control , Osteosarcoma/surgery , Photosensitizing Agents/chemistry , Photosensitizing Agents/toxicity , Porphyrins/chemistry , Porphyrins/toxicityABSTRACT
OBJECTIVE: To study the molecular mechanism of Zuogui Pill (ZGP) and Yougui Pill (YGP) on axonal regeneration in rats with experimental autoimmune encephalomyelitis (EAE). METHODS: EAE rat model was established by bilateral rear pedes subcutaneous injection of antigen made by mixing myelin basic protein (MBP) and complete Freud's adjuvant (CFA) in the volume ratio of 1:1. The pathological changes of axonal injury and regeneration in the brain and the spinal cord were observed on the 14th (the acute stage) and the 28th day (the remission stage) after modeling, with hematoxylin-eosin (HE) staining, silver stain, and immunohistochemical staining. The rats treated with prednisone acetate were taken as controls. RESULTS: Observation under the light microscope with HE staining showed a sleeve-like change in rats' cerebrospinal parenchyma with inflammatory cell infiltration around the small vessels and neuronic denaturation, while silver staining showed excessive tumefaction and abscission of axon, and immunohistochemical analysis showed decreasing of nerve growth factor (NGF) expression at the acute stage of EAE, which was even more remarkable at the remission stage, showing significant difference as compared with the normal control (P<0.05). And the expressions of Nogo A, an axon growth inhibitor, and its receptor (Nogo-66 receptor, Ng R) were significantly higher than those in the normal control at the acute stage (P<0.01). However, after the intervention of ZGP and YGP, the pathological changes and axon damage in rats' brain and spinal cord were much more alleviated, and the NGF expression was significantly higher than that in the model group at the acute stage (P<0.05). The expression of NGF was even stronger during the remission stage, and a better effect was shown by YGP. As for Nogo A and Ng R expressions, they were significantly lower than those in the model group at the acute stage (P<0.05), but a better effect was shown by ZGP. CONCLUSIONS: ZGP and YGP can prevent axonal injury and promote the axonal regeneration in rats of EAE, and the possible mechanism is to increase the expression of NGF and reduce the expression of Nogo A and its receptor. However, some differences are observed between the two Chinese preparations in their acting times and points, which provides a certain basis for revealing the modern connotation of the Chinese medicine theory on tonifying Shen ()-yin and Shen-yang.
Subject(s)
Axons/drug effects , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacology , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Nerve Regeneration/drug effects , Animals , Axons/metabolism , Axons/pathology , Axons/physiology , Brain/drug effects , Brain/metabolism , Brain/pathology , Disease Models, Animal , Drug Evaluation, Preclinical , Encephalomyelitis, Autoimmune, Experimental/metabolism , Encephalomyelitis, Autoimmune, Experimental/pathology , GPI-Linked Proteins , Male , Myelin Proteins/metabolism , Nerve Growth Factor/metabolism , Nogo Proteins , Nogo Receptor 1 , Rats , Rats, Inbred Lew , Receptors, Cell Surface , Receptors, Peptide/metabolism , Research , Signal Transduction/drug effects , TabletsABSTRACT
OBJECTIVE: To explore the functional effects of MAPK pathway in the pathogenesis of human osteosarcoma. METHODS: Gene microarray (Human Genome U133A, Affymetrix) was used to screen the differential expression of genes involved in MAPK pathway between osteosarcoma cell lines and 3 osteoblastic cell lines. KEGG metabolic pathway analysis was performed among significantly increased or decreased genes using the MATLAB software. Immunohistochemical technique was used to detect the expressions of ERK1/2, JNK and p38 proteins among 48 osteosarcoma and benign 24 osteoblastic tumor samples. RESULTS: Using an entrance limit of > or = 2.0, 18 differentially expressed MAPK pathway-related genes were selected (10 up-regulated, 8 down-regulated) to mapped to the MAPK pathway of KEGG which are all important node genes. The positive rates of ERK1/2, JNK and p38 proteins were 83.3% (40/48), 72.9% (35/48) and 85.4% (41/48) in osteosarcomas,and 12.5% (3/24), 8.3% (2/24) and 16.7% (4/24) in the control group, respectively. The positive rates and expression intensities were statistically different between the 2 groups (P<0.01). CONCLUSION: MAPK pathway plays an important role in the pathogenesis of osteosarcoma. ERK, JNK and p38 form an intercoordinating network and regulate the cell proliferation, differentiation, apoptosis, invasion and migration in osteosarcoma.
