OBJECTIVETo investigate the role of Chengqi Shengxue prescription in anti-tumor and immunoregulation and to evaluate its effect on apoptosis and T lymphocyte subsets of tumor-bearing mice.

METHODS180 ascites tumor and Lewis lung carcinoma tumor-bearing mice were used in the screening. Then 55 mice were treated randomly with the model, cyclophosphamide (30 mg x kg(-1)), or three different dosages of Chengqi Shengxue prescription (2. 4, 1.2, 0.6 g x kg(-1). After the treatment apoptosis of tumor cell and peripheral T lymphocyte subsets of tumor-bearing mice was analyzed by flow cytometry.

RESULTLewis lung carcinoma was a nsitive tumor cell line to Chengqi Shengxue prescription. Compared with the model group, significantly increased apoptosis was observed after administration of high and medium dose of Chengqi Shengxue prescription (P < 0. 05) by PI staining. Increased early apoptosis in cancer cells was observed in all experimental doses of Chengqi Shengxue prescription by Annexin V and PI double staining (P < 0.01) . The analysis of T lymphocyte subsets showed that the percentage of CD3, CD4 and CD4/CD8 ratio decreased significantly in model group when compared with the normal ones (P < 0.01), while no change was observed in CD8. In administration groups, CD3, CD4 and CD8 were significantly lower than normal ones (P < 0.01) , but CD4/CD8 ratio did not change significantly.

CONCLUSIONChengqi Shengxue prescription has selectively inhibitive effect on the growth of mouse Lewis lung carcinoma and takes an antitransfer role. Its anti-tumor effect may be owing to inducing tumor cell apoptosis. Chengqi Shengxue prescription improves cellular immune function through enhancing CD4/CD8 ratio.

Animals ; Antineoplastic Agents ; therapeutic use ; Apoptosis ; drug effects ; Carcinoma, Ehrlich Tumor ; drug therapy ; Carcinoma, Lewis Lung ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental ; drug therapy ; T-Lymphocyte Subsets ; drug effects ; immunology

OBJECTIVETo investigate the effects of Yiqi Chutan Recipe (YCR, a Chinese herbal prescription for invigorating qi and removing phlegm) on the growth and metastasis of tumor, survival time, and the expressions of peroxiredoxin (PRDX-1 and PRDX-6) in tumor tissue of C57BL/6J mice bearing Lewis lung carcinoma.

METHODSLewis lung carcinoma cells were transplanted to 90 C57BL/6J mice receiving preconditioning for inducing Pi-deficiency syndrome and divided into three groups treated respectively with saline, high dose YCR (3.0 g/kg) and low dose YCR (1.0 g/kg) once a day via gastric infusion. Besides, a group of 30 healthy mice simply received tumor cell transplantation was set up for controls. Ten mice selected from each group were sacrificed 21 days later, the size, weight and lung metastasis foci of tumor in mice were measured, and expressions of PRDX-1 and PRDX-6 in tumor tissue were detected using immunohistochemical method. The survival time of the remained 20 mice in each groups was observed.

RESULTSTumor size, weight and the numbers of lung metastatic foci were (1.14 +/- 0.30) cm3, (0.83 +/- 0.26) g, (6.20 +/- 2.53) foci in the high dose YCR treated group, which were significantly lower than those in the control group [(2.83 +/- 0.35) cm3, (2.08 +/- 0.28) g, and (8.60 +/- 1.84) foci] respectively, also lower than those in the saline treated group [(2.29 +/- 0.49) cm3, (1.67 +/- 0.33) g and (8.70 +/- 2.00) foci]. The median survival time in the three groups, in above order, were 29.00 +/- 0.89 days, 22.00 +/- 0.75 days and 21.00 +/- 0.53 days; the average survival time in them 29.60 +/- 0.53 days, 22.90 +/- 0.50 days and 20.95 +/- 0.44 days; the PRDX-1 expression were 0.15 +/- 0.03, 0.52 +/- 0.07 and 0.61 +/- 0.09; and the PRDX-6 expression were 0.12 +/- 0.02, 0.43 +/- 0.06 and 0.56 +/- 0.07, all showed significant difference in comparing the indices in the high dose treated group with those in the control group and in the saline treated group (P < 0.05 or P < 0.01). The tumor growth inhibition rate was 50.30% in the high dose YCR group with life prolongation rate of 41.29%, all better than those in the low dose YCR treated group (P < 0.05).

CONCLUSIONSYCR can remarkably inhibit the growth and metastasis of Lewis lung carcinoma in mice with Pi-asthenia syndrome, prolong their survival period, and its mechanism is possibly related to the reduction of over expressed PRDX-1 and PRDX-6.

Animals ; Carcinoma, Lewis Lung ; drug therapy ; metabolism ; pathology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Peroxiredoxin VI ; metabolism ; Peroxiredoxins ; metabolism

BACKGROUND AND OBJECTIVERadiation sensitivity is closely related to tissue oxygen, and rh-endostatin can induce the high level of oxygen content in tumor by "normalizing" tumor angiogenesis which is associated with radiotherapy sensitivity. The aim of this study is to observe the effect of combination of radiotherapy with rh-endostatin in the rats with lung cancer.

METHODSImmediate lewis cancerous ascetic injection method was used to make rats tumors bearing model, then the rats was divided into four groups randomly: group A was treated with saline; group B was treated with rh-endostatin; group C was treated with irradiation and group D was treated with rh-endostatin and irradiation. After all rats were treated, inhibition rates and the tumor growth curve were calculated. Immunohistochemisty was adopted to check the expressions of vascular endothelial growth factor (VEGF) and microvessel density (MVD).

RESULTSCompared with group A, the growth rates of the tumors in the other group were obviously slower, and the tumor weights were significantly different form group A (P < 0.05). Compared with the other groups, the tumor weights of group D were obviously reduced (P < 0.05). Compared with group A, VEGF and MVD of other three groups were reduced (P < 0.05), and group D were significantly cut down.

CONCLUSIONCombination with radiotherapy and rh-endostatin could inhibit the lung cancer significantly in rats. The possible mechanisms are to decrease the expression ofVEGF and inhibit the production of angiogenesis.

Animals ; Carcinoma, Lewis Lung ; drug therapy ; metabolism ; pathology ; radiotherapy ; Endostatins ; therapeutic use ; Female ; Immunohistochemistry ; Lung Neoplasms ; drug therapy ; metabolism ; radiotherapy ; Mice ; Mice, Inbred C57BL ; Microvessels ; pathology ; Random Allocation ; Vascular Endothelial Growth Factor A ; metabolism

OBJECTIVETo study the effects of polypeptide extract from scorpion venom (PESV) alliance with chemotherapy on angiogenesis of Lewis lung carcinomas (LLC) and its mechanism.

METHODLLC cells suspension (4 x 10(6) cells/mL) were subcutaneously injected into 54 C57BL/6J mice in right armpits. Then the tumor-bearing mice were randomly divided into three groups: the control group, the chemotherapy group and the PESV group. Cyclophosphamide was used to establish the model of cancer. Chemotherapy and PESV were added to the PESV group. Every 7 days, 6 mice of each group were executed, and the experiments were carried out for 28 days. The tumor volume and inhibitory rate were determined. Immunohistochemistry and RT-PCR were used to determine the expression of factor VIII, alpha-SMA, Dll4 and Notch1 in tumor tissue. Correlation analysis was used to identify the relationship of factor VIII and calculate microvessel density (MVD), alpha-SMA and vascular maturity.

RESULTThe inhibitory rate of PESV was 42.21%. Comparing with the chemotherapy group, the expression of tumor factor Dll4 and Notch1 in the PESV group were decreased significantly (P < 0.05). The expression of factor VIII and alpha-SMA in the chemotherapy group is lower than the control group (P < 0.05), while it's higher when compared with the PESV group (P < 0.01). Expression of Dll4 and Notch1 in the chemotherapy group at the 28th day were higher than the control group (P < 0.05), and the expression in the PESV group at the 21st day were significantly lower than the chemotherapy group (P < 0.05).

CONCLUSIONPESV could inhibit the angiogenesis of LLC. It might be attained by decreasing the level of angiogenic factors, that are factor VIII, alpha-SMA, Dll4 and Notch1 in tumor microenvironment.

Animals ; Antineoplastic Agents ; blood ; chemistry ; therapeutic use ; Carcinoma, Lewis Lung ; drug therapy ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred C57BL ; Neovascularization, Pathologic ; drug therapy ; Peptides ; chemistry ; therapeutic use ; Reverse Transcriptase Polymerase Chain Reaction ; Scorpion Venoms ; chemistry

OBJECTIVETo evaluate the anti-angiogenetic effect of the combination of low-dose cyclophosphamide(CTX) and ginsenoside Rg3 in mice with Lewis lung carcinoma, and to observe the anti-tumor effect, toxicity, adverse reaction of the treatment and survival time of the tumor bearing mice.

METHODSHolland C57/ BL6 Lewis lung carcinoma mice were taken as the model and randomly divided into 5 groups, i.e. the low-dose CTX (LDCTX) group, the maximum tolerable dose CTX (MTDCTX) group, the ginsenoside Rg3 (Rg3) group, the low-dose CTX combined with ginsenoside Rg3 group (LDCTX + Rg3), and the model group. Tumor volume, weight of mice, peripheral white blood cell counts and survival time of mice were observed, tumor microvascular density (MVD) and vascular endothelial growth factor (VEGF) gene expression were determined during the therapeutic course.

RESULTSIn the LDCTX group, tumor grew comparatively slow, no significant decrease in body weight or peripheral white blood cells, and survival time was prolonged. In the LDCTX + Rg3 group, the tumor inhibitory effect was more persistent and steady without any increase of toxicity or adverse reaction. Besides, the survival time of mice was prolonged (P < 0.01). MVD was lower in the LDCTX group than that in the MTDCTX group (P< 0. 05). Compared with the model group, MVD and VEGF expression were lower in the LDCTX and the Rg3 group, and the lowering action was more significant when the two drugs were used in combination (P < 0.05).

CONCLUSIONThe combination of low-dose CTX and Rg3 has obvious synergetic action of anti-angiogenesis, it shows significant and persistent tumor inhibitory effect, with less toxic and adverse reaction, and could induce longer survival time than treatment of CTX or Rg3 alone.

Angiogenesis Inhibitors ; therapeutic use ; Animals ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Carcinoma, Lewis Lung ; blood supply ; drug therapy ; pathology ; Cyclophosphamide ; administration & dosage ; Drug Therapy, Combination ; Female ; Ginsenosides ; therapeutic use ; Mice ; Mice, Inbred C57BL ; Neovascularization, Pathologic ; Random Allocation

OBJECTIVETo study the effect of Feiji Recipe (FR) intervening indoleamine 2,3-dioxygenase (IDO) induced immune escape on the murine model of Lewis lung carcinoma. Methods Totally 48 C57BL/6 mice inoculated with Lewis lung cancer cells transfected with human (enhanced green fluorescent protein,EGFP)-IDO gene were divided into four groups according to radom digit table, i.e., the model group (administered with normal saline by gastrogavage) , the Chinese medicine group (treated with FR Decoction at the daily dose of 100 mg/g by gastrogavage), the 1-methyl-D-trytaphan (1-MT) group (administered with 1-MT mixed liquor at the daily dose of 100 mg/kg by gastrogavage), and the Paclitaxel group (treated with Paclitaxel at the daily dose of 15 mg/kg by peritoneal injection), 12 in each group. The intervention was started from the 2nd day of modeling. The survival time was observed in 24 of them. Ratios of CD4+ CD25+ FoxP3+ regulatory T cells (Treg) in the spleen were detected in the rest 24 mice by flow cytometry respectively.

RESULTSCompared with the model group, the survival time was significantly prolonged in the Chinese medicine group and the 1-MT group (P < 0.01); ratios of Treg cells remarkably decreased in the Chinese medicine group, the 1-MT group, and the Paclitaxel group (P < 0. 01). Compared with the Paclitaxel group, the survival time was significantly prolonged in the Chinese medicine group and the 1-MT group (P < 0.01); ratios of Treg cells decreased significantly in the 1-MT group (P < 0.05).

CONCLUSIONFR could inhibit the proliferation of lung cancer cells and immune eseape, improve the immune function, and prolong the survival of tumor-bearing mice.

Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Carcinoma, Lewis Lung ; drug therapy ; immunology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase ; Lung Neoplasms ; Mice ; Mice, Inbred C57BL ; Paclitaxel ; T-Lymphocytes, Regulatory

OBJECTIVETo observe the effects of Lignum Sappan (LS) on the growth and metastases of transplanted Lewis lung carcinoma (LLC) in mice and investigate its partial mechanism of action.

METHODSC57BL/6 mice were established in LLC model and divided into six groups in random: Group A was untreated; Group B was treated by chemotherapy (CM) only; Groups C-F were treated respectively with low-dose LS, high-dose LS, CM + low-dose LS and CM + high-dose LS, via intragastric administration for 21 successive days. Mice were sacrificed in batches at different time points (d 7, d 14 and d 21) to observe the tumor inhibition rate and the metastases suppressing rate was measured dynamically. Meantime, the CD44 expression in tumor cells was measured by flow cytometry and serum P-selectin concentration was measured by ELISA assay.

RESULTSTumor weight in all treated groups, except Group C, was lower than that in Group A at the three time points (P < 0.05, P < 0.01), and that was lower in Group F than in Group B at the corresponding time points (P < 0.05, P < 0.01). Comparisons of CD44+ in tumor cells showed that as compared with Group A, on d 7, it was lower in Groups B and D (P < 0.01); on d 14, it was lower in Group E (P < 0.01) and Group F (P < 0.05); and on d 21, it was lower in Groups E and F (P < 0.01). As for the concentration of P-selectin, the intergroup comparisons showed that it was lower in Groups B-F on d 7 and in Group F on d 21 than that in Group A (P < 0.05 or P < 0.01), but showed insignificant difference in comparing the Group A with all the treated Groups on d 14 (P > 0.05).

CONCLUSIONLS and CM +LS could inhibit the growth and metastases of LLC, and shows inhibition on CD44 expression in tumor cells and P-selectin level in serum, which may be one of the mechanisms of LS in suppressing tumor metastasis.

Animals ; Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Caesalpinia ; chemistry ; Carcinoma, Lewis Lung ; drug therapy ; pathology ; Cell Proliferation ; drug effects ; Mice ; Mice, Inbred C57BL ; Neoplasm Metastasis ; prevention & control ; Phytotherapy ; Plant Extracts ; isolation & purification ; pharmacology ; therapeutic use ; Wood

OBJECTIVETo investigate the effect of mannatide injection (MI) in enhancing the efficacy of radiotherapy in two therapeutic schedules in mice bearing Lewis lung cancer.

METHODSC57BL/6 mice bearing Lewis lung cancer xenograft were assigned randomly into control group, fractionated schedule (FS) group, nonfractionated schedule (NFS) group, MI group, FS+MI group, and NFS+MI group (n=10). MI (4.5 mg/kg) or saline was given intraperitoneally for 14 consecutive days in the corresponding groups. Radiation with 8 MeV electron beam was delivered in a single 4 Gy dose in NFS and in 4 fractions (total dose 4 Gy) in FS. Tumor inhibition rate and the spleen and thymus index were calculated after the treatments.

RESULTSMI significantly enhanced the efficacy of radiotherapy with a tumor inhibition rate reaching 70% in FS+MI group (P<0.01). FS resulted in a significantly higher tumor inhibition rate than NFS (P<0.05), but the rates were comparable between FS+MI and NFS+MI groups. The spleen index and thymus indices were significantly higher in FS+MI and NFS+MI groups than in FS and NFS groups (P<0.05).

CONCLUSIONMI can enhance the efficacy of radiotherapy with different therapeutic schedules in mice bear Lewis lung cancer, and MI plus fractionated radiation produces the optimal effect.

Animals ; Biological Products ; therapeutic use ; Carcinoma, Lewis Lung ; drug therapy ; radiotherapy ; Combined Modality Therapy ; Dose Fractionation ; Dose-Response Relationship, Radiation ; Male ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Radiation-Sensitizing Agents ; therapeutic use ; Streptococcus

Honokiol is an active compound purified from magnolia that has been shown to induce cell differentiation, apoptosis, and anti-angiogenesis effects, as well as an enhancement in tumor growth delay in combination with chemotherapeutic agents in several mouse xenograft models. Our goal was to investigate the radiosensitization effect of honokiol on lung carcinoma. The radiosensitization effect of liposomal honokiol in Lewis lung carcinoma cells (LL/2) was analyzed using an in vitro clonogenic survival assay. For an in vivo study, Lewis lung carcinoma-bearing C57BL/6 mice were treated with either liposomal honokiol at 25 mg/kg or 5 Gy of single tumor radiation, or a combination of both over 12 days of treatment. The tumor growth delay and the survival time were evaluated. In addition, histological analysis of tumor sections was performed to examine changes by detecting the microvessel density and apoptosis in tumor tissues. In the clonogenic survival assay, LL/2 cells treated with IC50 Lipo-HNK for 24 h showed a radiation enhancement ratio of 1.9. After 12 days of combination treatment, the tumor volume decreased 78% and produced an anti-tumor activity 1.3-fold greater than a predicted additive effect of honokiol and radiation alone. This combination treatment also caused an 8.7 day delay in tumor growth. The cell cycle distribution and histological analysis demonstrated that liposomal honokiol has an anti-tumor effect via inducing apoptosis and inhibiting angiogenesis. Liposomal honokiol can enhance tumor cell radiosensitivity in vitro and in vivo, indicating that radiotherapy combined with liposomal honokiol can lead to greater anti-tumor efficacy.
Angiogenesis Inhibitors/administration & dosage/*therapeutic use ; Animals ; Apoptosis ; Biphenyl Compounds/administration & dosage/*therapeutic use ; Carcinoma, Lewis Lung/drug therapy/radiotherapy/*therapy ; Cell Cycle/drug effects/radiation effects ; Cell Line, Tumor ; Combined Modality Therapy ; Humans ; Lignans/administration & dosage/*therapeutic use ; Liposomes ; Lung Neoplasms/drug therapy/radiotherapy/*therapy ; Magnolia/chemistry ; Mice ; Neoplasm Transplantation ; Neovascularization, Pathologic/drug therapy/radiotherapy ; Radiation Tolerance ; Transplantation, Heterologous

OBJECTIVETo observe the effect of Yifei Qinghua Granule (YQG) on vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiostatin, and endostatin in tumor tissue of Lewis Lung cancer mice, and to explore its anti-tumor mechanisms.

METHODSTotally 70 C57BL/6 mice were randomly divided into the model group, the low, medium, and high dose YQG groups, the gefitinib group, the gefitinib plus medium dose YQG group, and the cyclophosphamide (CTX) group, 10 in each group. The models were established by subcutaneously injecting Lewis lung cancer cells from the right axilla of C57BL/6 mice. Mice in the model group were given with 0.4 mL pure water by gastrogavage, once daily. Mice in the low and medium dose YHG groups were given with YHG at the daily dose of 5 and 10 g/kg by gastrogavage, once daily. Those in the high dose YHG group were given with YHG at 10 g/kg by gastrogavage, twice daily. Those in the gefitinib group were given with gefitinib 100 mg/ kg by gastrogavage, once daily. Those in the gefitinib plus medium dose YHG group were given with gefitinib at 100 mg/kg by gastrogavage in the morning and YHG at 10 g/kg by gastrogavage in the afternoon. All medication was started from the 2nd day of inoculation, lasting 14 successive days. Those in the CTX group were given CTX at 60 mg/kg by peritoneal injection on the 3rd and the 7th day of the experiment. Mice were sacrificed at the fifteenth day of the experiment. Tumors were taken out. Expressions of VEGF, bFGF, angiostatin, and endostatin in the tumor tissue were detected using immunohistochemical assay.

RESULTSCompared with the model group, the expression of VEGF significantly decreased, expressions of angiostatin and endostatin significantly increased in each group (P < 0.01). The expression of bFGF significantly decreased in the gefitinib group (P < 0.05). There was no statistical difference in VEGF among all groups (P > 0.05). The angiostatin expression was significantly higher in the CTX group than in the low dose YQG group (P < 0.01). The expression of endostatin was significantly higher in the high dose YQG group and the gefitinib plus medium dose YQG group than in the low and the medium dose YQG groups (P < 0.01). The expression of endostatin was significantly higher in the gefitinib plus medium dose YQG group than in the gefitinib group (P < 0.05).

CONCLUSIONThe action mechanism of YQG in treating lung cancer might be achieved through reducing the expression of angiogenesis promoting factor VEGF and increasing expressions of angiogenesis inhibitors angiostatin and endostatin.

Angiostatins ; metabolism ; Animals ; Carcinoma, Lewis Lung ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Endostatins ; metabolism ; Fibroblast Growth Factor 2 ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Phytotherapy ; Vascular Endothelial Growth Factor A ; metabolism