OBJECTIVETo explore the effect and safety of topical propranolol hydrochloride gel for treatment of infantile hemangioma. METHODS Thirty nude mice (BALA/c, nu/nu) were divided into three groups, experimental group, control group and normal group. Human hemangioma endothelial cells cultured in vitro were injected subcutaneously in experimental group and control group to establish infantile hemangioma model. Topical propranolol hydrochloride gel was applied on the surface of the hemangioman in experimental group and normal group. Tumor volumn change and the skin situations (edema, erythema, ulceration) were observed at different periods. 45 days after cell injection, the mice were killed and plasma concentration was detected in the experimental group and the control group by high performance liquid chromatography with evaporative light scattering detector, and tumors were subjected to histopathologic examination and immunohistochemistry for CD31 and CD34. The correlation between volumes and plasma concentration was statistically analyzed with SPSS 13.0 paired samples t test with α = 0.05 as statistical standard.

RESULTSAt 45 days, the volume of the tumor in control group was (366.57 ± 17.08) mm³, which has a significant difference as compared to the experimental group (13.36 ± 2.09) mm³ (P < 0.05); and the plasma concentration was (16.83 ± 1.53) ng/ml in experimental group, and (18.42 ± 2.21) ng/ ml in normal group (P > 0.05 ). Topical propranolol hydrochloride gel (3%) has no irritation to nude mice's skin.

CONCLUSIONSTopical application of 3% propranolol hydrochloride gel is effective and safe for the treatment of infantile hemangioma.

Animals ; Gels ; administration & dosage ; Hemangioma ; drug therapy ; pathology ; Humans ; Immunohistochemistry ; Mice ; Mice, Nude ; Propranolol ; administration & dosage ; Skin Neoplasms ; drug therapy ; pathology ; Tumor Burden ; drug effects

OBJECTIVE: The aim of this study is to investigate the effects of inhibitor HNP1 transfection on proliferation and tumor growth of human nasopharyngeal carcinoma cell line HNE1. METHOD: HNE1 cells were transfected with HNP1 by liposome, and the cytotoxic effect was detected by MTT, In vivo tumor growth test was performed in nude mice inoculated with transfected HNE1 cells. The therapeutic effect of HNP1 was evaluated in the inoculated tumors, alpha-defensin 1 expression was detected in implanted tumor tissues by immunohistochemical stain. RESULT: HNP1 transfection significantly inhibited the proliferation of HNE1 cells. MTT assay confirmed cytotoxic effect. In vivo study showed tumor volume was significantly smaller in HNP1 transfection group than that in control group (P < 0.01). Immunohistochemical stain showed alpha-defensin expression was increased in HNP1 transfection group. CONCLUSION HNP1 transfection can inhibit the proliferation of HNE1 cells, as well as tumor growth.
Animals ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Female ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Nasopharyngeal Neoplasms ; genetics ; pathology ; Transfection ; Tumor Burden ; alpha-Defensins ; genetics

OBJECTIVE: To summarize and critically assess the inhibitory effects of Chinese herbal medicine (CHM) on tumor volume and tumor weight for the treatment of osteosarcoma (OS) in mouse models. METHODS: PubMed, Embase, Web of Science, China Knowledge Resource Integrated Database (CNKI), Wanfang Database, VIP Database, and Chinese BioMedical (CBM) were searched since their inception dates to March 10, 2016. Two reviewers independently selected the controlled studies estimating effects of CHM on mouse OS by administration in vivo. A pair-wise meta-analysis was performed. Twenty-five studies with adequate randomization were included in the systematic review. RESULTS: CHM may significantly inhibit OS growth in mice, as assessed using the tumor weight [20 studies, n=443; 290 for CHM and 153 for the control: pooled mean difference (MD)=-2.90; 95% confidence interval (Cl): -3.50 to -2.31: P<0.01], tumor volume (16 studies, n=382; 257 for CHM and 125 for the control; pooled MD =-2.57; 95% Cl: -3.33 to -1.80; P<0.01) and tumor growth inhibition rate. CONCLUSION CHM could significantly inhibit the growth of OS in mouse models, which might be supportive for the design of preclinical and clinical trials in future.
Animals ; Drugs, Chinese Herbal ; therapeutic use ; Mice ; Osteosarcoma ; drug therapy ; Publication Bias ; Risk Factors ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

OBJECTIVETo explore the molecular mechanism of γ-aminobutyric acid (GABA) inhibitory on the growth of cholangiocarcinoma cell line (QBC939).

METHODSQBC939 cells were cultured in different groups and treated with GABA, GABA + bicuculine (A receptor antagonist), GABA + phaclofen (B receptor antagonist) for 48 hours. MTT assay was used to determine the proliferation of QBC939 cells. Annexin V-FITC/PI binding assay was used to detect apoptosis in the QBC939 cells. Western blot was applied to check the expression of signal transducer and activator of transcription 3 (STAT3) and phosphorylation-STAT3 (p-STAT3) proteins in different groups of QBC939 cells. Animal models of cholangiocarcinoma bearing nude mice were established by subcutaneous injection of QBC939 cells and randomized into 2 groups: control and GABA-treated groups. The effect of GABA was evaluated after 5 weeks, including the body weight and tumor volume. The expression of p-STAT3 was detected by immunohistochemistry and Western blot in xenograft tumors.

RESULTSMTT and FCM assays both showed that the effect of GABA inhibitory on the proliferation (15.30% ± 0.80% vs. 2.66% ± 0.74%, t = 23.15, P = 0.00) and induced apoptosis (23.15% ± 0.21% vs. 4.30% ± 0.69%, t = 52.40, P = 0.00) of QBC939 cells could be antagonized by phaclofen, but not bicuculine. The expression of STAT3 and p-STAT3 proteins were all observed in the QBC939 cells and GABA significantly down-regulated p-STAT3 protein expression (0.77 ± 0.00 vs. 0.45 ± 0.01, t = 63.14, P = 0.00), this action was also antagonized by phaclofen (0.45 ± 0.01 vs. 0.76 ± 0.01, t = 56.25, P = 0.00). Xenograft tumor volume ((0.62 ± 0.03) cm³ vs. (0.34 ± 0.03) cm³, t = 13.45, P = 0.00) and the expression of p-STAT3 protein were significantly decreased in GABA-treated group as compared with control group.

CONCLUSIONSGABA may inhibit the growth of cholangiocarcinoma cells QBC939 through GABA(B) receptor, and down-regulation of the p-STAT3 expression perhaps is one of its anti-tumor mechanisms.

Animals ; Apoptosis ; drug effects ; Bile Duct Neoplasms ; pathology ; Bile Ducts, Intrahepatic ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cholangiocarcinoma ; pathology ; Humans ; Mice ; Mice, Nude ; STAT3 Transcription Factor ; metabolism ; Tumor Burden ; gamma-Aminobutyric Acid ; pharmacology

OBJECTIVETo investigate the changes of serum inteferon-gamma (IFN-gamma) in mice bearing S-180 tumor and explore the role of the endogenous IFN-gamma in confining the transplanted tumor by intervention with immunomodulators.

METHODSMouse models bearing S-180 solid tumor were established and subjected to intragastric administration of Ganoderma lucidum polysaccharides (GLP) or cyclosporine A (CsA) at different daily doses for 9 consecutive days. Serum IFN-gamma levels were measured in untreated tumor-bearing mice and in those after completion of GLP or CsA treatments by enzyme-linked immunosorbent assay (ELISA), and the changes of the tumor weight in the treated mice were evaluated.

RESULTSIt was found for the first time that serum IFN-gamma levels in the tumor-bearing mice increased progressively within the initial 20 days after tumor implantation. The serum IFN-gamma levels in the 3 GLP-treated groups (at daily doses of 400, 200, and 100 mg/kg) all increased, which was the most obvious in 400 mg/kg GLP-treated group, and the tumor weight decreased significantly in response to GLP treatment, but the most conspicuous effect occurred with the daily dose of 200 mg/kg, and no significant statistical correlation was found between the two parameters. CsA treatment (at 20, 10, and 5 mg/kg, respectively) resulted in reduced serum IFN-gamma levels but produced virtually no effect on the tumor weight, and no obvious correlation was found between serum IFN-gamma level and the tumor weight.

CONCLUSIONIncreased serum IFN-gamma levels following GLP treatment are not significantly correlated to tumor growth inhibition in mice, and CsA reduces serum IFN-gamma levels without affecting the tumor weight, suggesting that endogenous IFN-gamma is not a major immunomodulating factor in growth inhibition of transplanted S-180 tumor.

Animals ; Cyclosporine ; pharmacology ; Female ; Ganoderma ; chemistry ; Immunologic Factors ; pharmacology ; Interferon-gamma ; blood ; Male ; Mice ; Polysaccharides ; pharmacology ; Sarcoma 180 ; blood ; pathology ; prevention & control ; Tumor Burden ; drug effects

OBJECTIVETo investigate effect of lysophosphatidic acid (LPA) on growth and metastasis of intraperitonally transplanted tumor in nude mice.

METHODSSixteen nude mice randomly divided into control group and LPA treatment group, in which 6x10(6) untreated and LPA-treated human ovarian cancer cells skov3 were respectively transplanted intraperitoneally. After death of the nude mice without interventions, the weight of the transplanted tumors and number of metastatic tumors were recorded.

RESULTSThe rate of tumor formation was 100%in both groups, but the treatment group showed more rapid tumor growth, greater tumor weight and more numerous metastatic tumors than the control group (P<0.01).

CONCLUSIONLPA simulates the growth and promotes invasiveness of transplanted ovarian cancer cells in the peritoneal cavity of nude mie.

Animals ; Female ; Lysophospholipids ; toxicity ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Neoplasm Transplantation ; Ovarian Neoplasms ; pathology ; Peritoneal Neoplasms ; chemically induced ; secondary ; Random Allocation ; Transplantation, Heterologous ; Tumor Burden ; drug effects

The in vitro release behavior, in vivo biodistribution and antitumor activity of N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-5-fluorouracil conjugates (P-FU) were studied. The in vitro release behavior was evaluated by determining the amount of 5-fluorouracil (5-FU) released from P-FU in mice plasma at 37 degrees C. The in vivo biodistribution and therapeutic evaluation were investigated with Kunming mice bearing hepatoma 22 (H22). The in vitro half-life (t1/2) of P-FU in mice plasma was 32.4 h. It appeared that the circulation life time of the conjugates were 166 times longer than that of 5-FU. The AUC and t1/2 of P-FU in tumor were 3.3 times and 2.3 times more than those of 5-FU, respectively. Therapeutic evaluation also demonstrated that the treatment with P-FU displayed stronger inhibition of the tumor growth when compared with that of 5-FU (P < 0.05). HPMA copolymer is a potential carrier for 5-FU for effective treatment of cancer.
Acrylamides ; pharmacokinetics ; pharmacology ; Animals ; Antimetabolites, Antineoplastic ; pharmacokinetics ; pharmacology ; Area Under Curve ; Cell Line, Tumor ; Drug Carriers ; Drug Compounding ; Female ; Fluorouracil ; pharmacokinetics ; pharmacology ; Liver Neoplasms, Experimental ; metabolism ; pathology ; Mice ; Neoplasm Transplantation ; Random Allocation ; Tissue Distribution ; Tumor Burden ; drug effects

OBJECTIVETo investigate the effects of peptide YY (PYY) on subcutaneous transplantation tumor of human hepatoma in nude mice and preliminarily explore the mechanisms.

METHODSHepG2 human hepatic carcinoma cells were injected into nude mice subcutaneously, and the resultant tumor were taken and prepared into small tissue blocks. The tissue blocks were implanted subcutaneously into nude mice to establish mouse models bearing human hepatoma. Thirty-two such mouse models were assigned equally into 4 groups to receive subcutaneous PYY injection at a high or low dose, intraperitoneal injection of floxuridine (positive control group), or subcutaneous normal saline injection (negative control group). The general condition of the tumor-bearing mice and the growth of the tumors were observed.

RESULTSCompared with the negative control group, the high- and low-dose PYY groups showed reduced gross tumor volume, lowered serum AFP, tumor weight, and cAMP content in the tumor tissue (P<0.05).

CONCLUSIONPYY can inhibit the growth of subcutaneous hepatoma in nude mice, which might be associated with the reduction of cAMP content in the tumors following PYY treatment.

Animals ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Cell Line, Tumor ; Cyclic AMP ; metabolism ; Humans ; Liver Neoplasms, Experimental ; drug therapy ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Peptide YY ; therapeutic use ; Tumor Burden ; drug effects ; Xenograft Model Antitumor Assays

OBJECTIVETo study the radiosensitizing effect of resveratrol on human hypo pharyngeal squamous cell carcinoma (FaDu) cells in nude mice.

METHODSForty-three nude mice bearing FaDu cell xenografts were randomized into control group, radiotherapy (12 Gy) group, resveratrol treatment (50 mg/kg) group, and radiotherapy plus resveratrol treatment group. After corresponding treatments, the tumor volume in the mice was measured every 3 days, and the microvessel density (MVD) in the tumor was evaluated with CD31 immunofluorescence histochemical staining.

RESULTSThe tumor volume and weight were the smallest in mice receiving radiotherapy plus resveratrol treatment (P<0.05) but comparable between those having resveratrol treatment alone and the control mice. Radiotherapy plus resveratrol treatment resulted in a tumor inhibition rate of 76.64% and a significantly decreased MVD in the tumor compared with the other 3 groups.

CONCLUSIONResveratrol can produce a radiosensitizing effect on human hypopharyngeal carcinoma in nude mice.

Animals ; Carcinoma, Squamous Cell ; drug therapy ; radiotherapy ; Cell Line, Tumor ; radiation effects ; Head and Neck Neoplasms ; drug therapy ; radiotherapy ; Humans ; Hypopharyngeal Neoplasms ; drug therapy ; radiotherapy ; Mice ; Mice, Nude ; Radiation Tolerance ; Radiation-Sensitizing Agents ; pharmacology ; Stilbenes ; pharmacology ; Transplantation, Heterologous ; Tumor Burden

OBJECTIVETo observe the in vivo effects of oxysophoridine on hepatocellular carcinoma in mice and to study the related mechanisms.

METHODSC57BL mice were inoculated with mouse hepatoma H22 cells subcutaneously, then divided into 5 groups (14 per group), and treated with oxysophoridine (50, 100, or 150 mg/kg) or cisplatin (4 mg/kg) for 10 days. Inhibitory rate of tumor, body weight gain, and influence indices on internal organs (liver, spleen and thymus) were evaluated. The differentially expressed genes between the oxysophoridine-treated group, and the control group were analyzed using cDNA microarray and quantitative real-time PCR (qRT-PCR) experiments.

RESULTSCompared with the tumor weight of the control group (2.75±0.66 g), oxysophoridine significantly suppressed hepatocellular carcinoma growth in mice (P <0.01), with 0.82±0.36 g, 0.57±0.22 g, and 1.22±0.67 g for the tumor weight in the low, moderate, and high dose treatment group, respectively. The moderate dose led to the highest inhibitory rate, 79.3%. Observation of body weight gain and influence on three organs showed that compared with cisplatin, oxysophoridine produced fewer side effects in vivo. cDNA microarray and qRT-PCR showed that the most significant differentially expressed genes in the tumor samples of oxysophoridine-treated mice were mostly involved in regulating apoptosis, with the Tnfrsf11b (osteoprotegerin) gene being the most significantly affected.

CONCLUSIONOxysophoridine was a promising compound for developing drugs against hepatocellular carcinoma, and its anti-hepatoma effect was probably related to osteoprotegerin activation.

Alkaloids ; pharmacology ; Animals ; Carcinoma, Hepatocellular ; genetics ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Screening Assays, Antitumor ; Gene Expression Regulation, Neoplastic ; drug effects ; Liver Neoplasms, Experimental ; genetics ; pathology ; Mice ; Mice, Inbred C57BL ; Oligonucleotide Array Sequence Analysis ; Organ Specificity ; drug effects ; Real-Time Polymerase Chain Reaction ; Tumor Burden ; drug effects ; Weight Gain ; drug effects