This study aims to establish the S_(180) tumor-bearing mice model, and to investigate the influence of Shenqi Erpi Granules(SQEPG) on immune function, as well as the drug's tumor-suppressive effect and mechanism. SPF grade KM mice(half male and half female) were randomly divided into 6 groups: a control group, a model group, a cyclophosphamide group(50 mg·kg~(-1)), as well as SQEPG groups in low-, medium-, and high-dose(5.25, 10.5, 21 g·kg~(-1)). The control group and the model group were given distilled water, and the other 4 groups were given the corresponding drugs by gavage. The administration continued for 10 days before the mice were sacrificed. The antitumor and immune regulation effects of SQEPG were evaluated. The effect of SQEPG on delayed type hypersensitivity reaction(DTH), carbon clearance index, and serum hemolysin antibody level was observed to reflect the effect on the immune function of tumor-bearing mice. Tumor weight was recorded to calculate the tumor suppression rate and the immune organ index. Hematoxylin-eosin(HE) staining was used to detect morphological changes in tumor tissues. Flow cytometry was employed to detect the percentage of CD4~+ and CD8~+ T-cells in the spleen tissues and the tumor tissue apoptosis levels. Immunohistochemistry was conducted to detect the KI67 protein expression level of tumor tissues. ELISA resorted to the detection of the following expression levels in tumor tissues: tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), interferon-γ(IFN-γ). Western blot was performed to detect the expression levels of caspase-3, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinases 4(CDK4), G_1/S-specific cyclin D1(cyclin D1), and vascular endothelial growth factor A(VEGFA). The results showed that, compared with the model group, the SQEPG could increase the swelling of the auricle of the tumor-bearing mice; significantly increase the phagocytic index of carbon granule contour(P<0.05 or P<0.01), and the middle dose of SQEPG could significantly increase the antibody level of hemolysin(P<0.05); different doses of SQEPG significantly inhibit the growth of the tumor, and decrease the mass of the tumor tissues(P<0.05 or P<0.01); the low dose of SQEPG significantly decreased spleen index(P<0.05), low and high doses of SQEPG increased thymus index, while medium doses of SQEPG decreased thymus index. High doses of SQEPG significantly elevated the levels of CD4~+ and CD8~+ T-cells in the spleens of the homozygous mice(P<0.01 or P<0.001), and increased the apoptosis rate of the cells of the tumor tissues(P<0.05); Meanwhile, high-dose SQEPG elevated the levels of immunity factors such as IL-2, IFN-γ and TNF-α in the serum of tumor-bearing mice(P<0.01); medium-and high-dose SQEPG significantly lowered the rate of positive expression of KI67 protein in tumor tissues(P<0.01). Compared with the model group, high-dose SQEPG significantly up-regulated the expression of caspase-3 and Bax proteins in tumor tissues(P<0.05), and significantly down-regulated the expression of CDK4, cyclin D1, and VEGFA proteins(P<0.05 or P<0.01). In conclusion, SQEPG has the effect of improving immune function and inhibiting tumor growth in tumor-bearing mice. Its mechanism of tumor-suppressive effects may be related to apoptosis promotion, cell cycle progression block, and tumor cell proliferation inhibition.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Male ; Female ; Apoptosis/drug effects* ; Sarcoma 180/genetics* ; Humans

OBJECTIVE: To explore the antitumor effects of ethanol extract from Ventilago leiocarpa Benth (EEVLB) on sarcoma 180 (S180) tumor-bearing mice and the potential mechanism. METHODS: Sixty mice were randomly assigned to 6 groups according to a random number table: normal group, model group, 5-fluorouracil (5-FU) group (0.02 g·kg RESULTS: EEVLB with different concentrations achieved inhibition of tumor growth in vivo, wherein the high-dose group showed the most significant reduction in tumor weight and increased apoptosis of tumor cells (P<0.05). In addition, both net weight gain and spleen index of mice showed uptrend in EEVLB treatment groups (P<0.05). Besides, serum levels of IL-2 and IL-6, percentages of CD3 CONCLUSIONS EEVLB exhibits promising antitumor activity in vivo. This effect might be due to activation of apoptotic signaling pathway, increase of cytokine levels and enhancement of immune function in tumor-bearing mice.
Animals ; Cell Line, Tumor ; Ethanol ; Mice ; Plant Extracts/therapeutic use* ; Rhamnaceae ; Sarcoma 180/drug therapy*

Korl:ICR mice, established by the Korean National Institute of Food and Drug Safety Evaluation (NIFDS), are characterized based on their genetic variation, response to gastric injury, and response to constipation inducers. To compare the inhibitory responses of ICR stocks obtained from three different sources to the anticancer drug cisplatin (Cis), alterations in tumor volume, histopathological structure, and toxicity were examined in Sarcoma 180 tumor-bearing Korl:ICR, A:ICR (USA source), and B:ICR (Japan source) mice treated with low and high concentrations of Cis (L-Cis and H-Cis, respectively). Tumor size and volume were lower in H-Cis-treated mice than in L-Cis-treated mice in all three ICR stocks with no significant differences among stocks. There was a significant enhancement of the necrotizing areas in the histological structures in the L-Cis- and H-Cis-treated groups relative to that in the untreated group. The necrotizing area changes were similar in the Sarcoma 180 tumor-bearing Korl:ICR, A:ICR, and B:ICR mice. However, there were stock-bases differences in the serum biomarkers for liver and kidney toxic effects. In particular, the levels of AST, ALT and BUN increased differently in the three H-Cis-treated ICR stocks, whereas the levels of ALP and CRE were constant. Taken together, the results of the present study indicate that Korl:ICR, A:ICR, and B:ICR mice have similar overall inhibitory responses following Cis treatment of Sarcoma 180-derived solid tumors, although there were some differences in the magnitude of the toxic effects in the three ICR stocks.
Animals ; Biomarkers ; Cisplatin ; Constipation ; Genetic Variation ; Kidney ; Liver ; Mice ; Mice, Inbred ICR* ; Sarcoma ; Sarcoma 180 ; Tumor Burden

In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size (mean diameter of 100.2 +/- 15.2 nm), a homogeneous distribution [the polydispersity index was (0.251 +/- 0.018)] and high encapsulation efficiency (90.15 +/- 2.47) % and (80.64 +/- 3.52) % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route.
ATP-Binding Cassette, Sub-Family B, Member 1 ; antagonists & inhibitors ; Administration, Oral ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; pharmacology ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; pharmacology ; Drug Carriers ; chemistry ; Female ; Liposomes ; chemistry ; Male ; Mice ; Nanoparticles ; Neoplasm Transplantation ; Paclitaxel ; administration & dosage ; pharmacokinetics ; pharmacology ; Particle Size ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sarcoma 180 ; pathology ; Silicon Dioxide ; chemistry ; Tumor Burden ; drug effects

The anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes (FA-PDCT-L) was investigated in vitro and in vivo. FA-PDCT-L was prepared by organic solvent injection method. Transmission electron microscope, dynamic light scattering and electrophoretic light scattering were employed to study the physicochemical parameters of FA-PDCT-L. The inhibitory effects of docetaxel injection (DCT-I), non-modified DCT liposomes (DCT-L) and FA-PDCT-L on the growth of MCF-7 and A-549 cells at different incubation times were detected by CCK-8 assay; and the hemolytic test was employed in vitro. Tumor mice were randomized into 4 groups: DCT-I, DCT-L, FA-PDCT-L and control group (normal saline), and given drugs at 10 mg x kg(-1) x d(-1) through tail vein. The tumor volume, mice weight, inhibition rate of tumor and life span were measured at the end of experiments. The IC50 of the FA-PDCT-L for MCF-7 and A549 cell lines were significantly lower than that of DCT-I and DCT-L, without hemolysis reaction observed. Compared with control group, the weights of tumor in DCT-I, DCT-L and FA-PDCT-L were decreased, especially for FA-PDCT-L, with inhibitory rates at 79.03 % (P < 0.05). The life span and median survival time of FA-PDCT-L treated mice were significantly higher than that of DCT-I and DCT-L. In conclusion, FA-PDCT-L shows a good anti-tumor activity, indicating that it is potential carriers for DCT in the treatment of tumor.
Animals ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyanoacrylates ; chemistry ; Drug Carriers ; Female ; Folate Receptors, GPI-Anchored ; chemistry ; Humans ; Inhibitory Concentration 50 ; Liposomes ; chemistry ; Lung Neoplasms ; pathology ; MCF-7 Cells ; Mice ; Neoplasm Transplantation ; Particle Size ; Polyethylene Glycols ; chemistry ; Rabbits ; Random Allocation ; Sarcoma 180 ; pathology ; Taxoids ; administration & dosage ; pharmacology ; Tumor Burden ; drug effects

To study the toxicity-decreasing and synergistic effect of intracellular and extracellular polysaccharides from Phellinus igniarius on S180 mice. The PIP and PIE were extracted from the products of liquid submerged fermentation of P. igniarius. Transplanting S180 mice tumor models were established so as to observe the changes in tumor inhibiting rate, indexes of the spleen and thymus, body weight, peripheral blood cells and IFN-gamma levels when CTX was used alone and when used in combination with the PIP and PIE from P. igniarius. The results indicate that the PIP and PIE from P. igniarius can increase the activity of body immunity, attenuate the toxicity of CTX as well, and improve the anti-tumor effects.
Animals ; Antineoplastic Agents ; isolation & purification ; pharmacology ; Basidiomycota ; chemistry ; classification ; isolation & purification ; Body Weight ; drug effects ; Cyclophosphamide ; pharmacology ; Disease Models, Animal ; Drug Synergism ; Female ; Interferon-gamma ; blood ; Male ; Medicine, Chinese Traditional ; Mice ; Neoplasm Transplantation ; Plant Extracts ; Polysaccharides ; isolation & purification ; pharmacology ; Random Allocation ; Sarcoma 180 ; drug therapy ; pathology ; Spleen ; pathology ; Thymus Gland ; pathology

OBJECTIVETo detect the effect of GFW on tumor cell metastasis in S180 tumor-bearing mice.

METHODS180 tumor-bearing mice model were replicated and divided randomly into 4 groups: the model group, the GFW group, the cyclophosphamide group and the combination administration group. VEGF in serum on each group was detected by ELISA, and the expression of metastasis suppressor gene nm23H1 and cell adhesion molecule CD44 in Sarcoma were detected by SABC immunohistochemical assay.

RESULTCompared with the model group, the GFW group showed a significant decrease in VEGF in serum (P < 0.01). From their statistically significant difference, GFW was proved to promote the expression of metastasis suppressor gene nm23H1 and inhibit the expression of cell adhesion molecule CD44 (P < 0.05).

CONCLUSIONGFW has an effect on inhibiting tumor metastasis to some extent.

Animals ; Antineoplastic Agents ; pharmacology ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Regulation, Neoplastic ; drug effects ; Hyaluronan Receptors ; metabolism ; Male ; Mice ; Neoplasm Metastasis ; Sarcoma 180 ; blood ; metabolism ; pathology ; Vascular Endothelial Growth Factor A ; blood ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the effects of sphingosine-1-phosphate (S1P) on cyclophosphamid (CTX) and cisplatin (DDP)-induced ovarian damage and on the efficacy of chemotherapy in mice bearing S180 murine sarcoma.

METHODSFifty-two female C57BL/6 mice were randomized into normal control group (n=10), tumor-bearing model group (n=14), CTX+DDP group (n=14), and S1P+CTX+DDP group (n=14). Before medication and on day 11 of medication during diestrus stage, the mice were sacrificed to measure the ovarian weight, numbers of primordial follicles and growing follicles, tumor weight, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol ( E2).

RESULTSAt day 11 of medication, the levels of serum FSH and E2, but not LH, showed significant differences in CTX+DDP group from those in the other groups (P<0.01). FSH, E2, and LH levels were comparable between S1P+CTX+DDP group and the control group (P>0.05). The number of primodial follicles and weight of ovaries in CTX+DDP group decreased significantly compared to those in the other groups (P<0.01). The number of growing follicles in CTX+DDP group was significantly lower than that in the control and model groups(P<0.01), but similar to that in S1P group (P>0.05). The number of primodial follicles and growing follicles and ovarian weight in S1P+CTX+DDP group were close to those in the control and model groups (P>0.05). In CTX+DDP and S1P+CTX+DDP groups, the tumor weight were significantly lower than that in the other two groups (P<0.01), and the tumor inhibition rates were both higher than 60%.

CONCLUSIONS1P can ameliorate chemotherapy-induced ovarian damage in mice without affecting the efficacy of chemotherapy.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Cisplatin ; administration & dosage ; adverse effects ; Cyclophosphamide ; administration & dosage ; adverse effects ; Female ; Lysophospholipids ; therapeutic use ; Mice ; Mice, Inbred C57BL ; Primary Ovarian Insufficiency ; chemically induced ; prevention & control ; Sarcoma 180 ; drug therapy ; Sphingosine ; analogs & derivatives ; therapeutic use

This study was initiated in order to investigate the anticancer and immunomodulating activities of crude polysaccharides extracted in methanol, neutral saline, and hot water (hereinafter referred to as Fr. MeOH, Fr. NaCl, and Fr. HW, respectively) from the fruiting bodies of Panellus serotinus. Content of beta-glucan and protein in Fr. MeOH, Fr. NaCl, and Fr. HW extracts of P. serotinus ranged from 22.92~28.52 g/100 g and 3.24~3.68 g/100 g, respectively. In vitro cytotoxicity tests, none of the various fractions of crude polysaccharides were cytotoxic against sarcoma 180, HT-29, NIH3T3, and RAW 264.7 cell lines at the tested concentration. Intraperitoneal injection with crude polysaccharides resulted in a life prolongation effect of 23.53~44.71% in mice previously inoculated with sarcoma 180. Treatment with Fr. HW resulted in an increase in the numbers of spleen cells by 1.3 fold at the concentration of 50 microg/mL compared with control. Treatment with Fr. NaCl resulted in improvement of the immuno-potentiating activity of B lymphocytes by increasing the alkaline phosphatase activity by 1.4 fold, compared with control, at the concentration of 200 microg/mL. Among the three fractions, maximum nitric oxide (13.48 microM) was recorded at 500 microg/mL in Fr. HW. Production of tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 was significantly higher, compared to the positive control, concanavalin A, at the tested concentration. Therefore, treatment with crude polysaccharides extracted from the fruiting body of P. serotinus could result in improvement of antitumor activity.
Alkaline Phosphatase ; Animals ; B-Lymphocytes ; Cell Line ; Concanavalin A ; Fruit ; Injections, Intraperitoneal ; Interleukin-1beta ; Interleukin-6 ; Life Support Care ; Methanol ; Mice ; Nitric Oxide ; Polysaccharides ; Sarcoma 180 ; Spleen ; Tumor Necrosis Factor-alpha ; Water

Pleurotus nebrodensis is an edible and commercially available mushroom in Korea. This study was conducted in order to evaluate the anticancer and immunopotentiating activities of crude polysaccharides, extracted in methanol, neutral saline, and hot water (hereafter referred to as Fr. MeOH, Fr. NaCl, and Fr. HW, respectively) from the fruiting bodies of P. nebrodensis. beta-Glucan and protein contents in Fr. MeOH, Fr. NaCl, and Fr. HW extracts of P. nebrodensis ranged from 23.79~36.63 g/100 g and 4.45~6.12 g/100 g, respectively. Crude polysaccharides were not cytotoxic against sarcoma 180, HT-29, NIH3T3, and RAW 264.7 cell lines at a range of 10~2,000 microg/mL. Intraperitoneal injection with crude polysaccharides resulted in a life prolongation effect of 11.76~27.06% in mice previously inoculated with sarcoma 180. Treatment with Fr. NaCl resulted in an increase in the numbers of spleen cells by 1.49 fold at the concentration of 50 microg/mL, compared with control. Fr. HW improved the immuno-potentiating activity of B lymphocytes through an increase in alkaline phosphatase activity by 1.65 fold, compared with control at 200 microg/mL. Maximum production of nitric oxide (14.3 microM) was recorded in the Fr. NaCl fraction at 200 microg/mL. Production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) was significantly higher, compared to control, and IL-6 production was highest, in contrast to TNF-alpha, IL-1beta, and positive control, concanavalin at the tested concentration of the various fractions. Results of the current study suggest that polysaccharides extracted from P. nebrodensis have a strong anticancer effect and may be useful as an ingredient of biopharmaceutical products for treatment of cancer.
Agaricales ; Alkaline Phosphatase ; Animals ; B-Lymphocytes ; Cell Line ; Fruit ; Immunomodulation ; Injections, Intraperitoneal ; Interleukin-1beta ; Interleukin-6 ; Korea ; Life Support Care ; Methanol ; Mice ; Nitric Oxide ; Pleurotus ; Polysaccharides ; Sarcoma ; Sarcoma 180 ; Spleen ; Tumor Necrosis Factor-alpha ; Water