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Objective To investigate the differences in susceptibility to Lewis lung carcinoma and T lymphocyte subsets in the immune microenvironment between young and elderly mice.Methods Six C57/B6 mice at two months(young)and six mice at twelve months(aged)were injected with Lewis lung carcinoma cells at the dose of 1 × 106 in the left armpit to establish a murine model of lung carcinoma.The weight and tumor growth were monitored.Blood samples for routine blood tests were collected after 24 days.The proportions of CD4+ and CD8+T cells in the spleen were detected by flow cytometry,and the infiltration of CD4+,CD8+ T cells and related effector T cells in the tumor microenvironment were determined in the same way.Results The body weight of tumor bearing mice in the aged group was significantly higher than that in the young group(P ＜0.001);The tumor weight in the aged group(5.084±0.528)g was significantly higher than that in the young group(2.963 ±0.378)g(t =3,349,P =0.012);Routine blood tests showed that the numbers of leukocytes and subsets(except mononuclear)in the aged group were significantly lower than in the young group(P ＜0.05);Flow cytometry found that the effector and memory/effector CD4+T cell ratios in the spleen were significantly higher in the aged group than in the young group(P ＜0.001)and the expression of effector and memory/effector CD8+T cells in the tumor microenvironment was also significantly higher than in the young group(P ＜0.05);Quantitative expression values of IL-6 and IL-10 in the tumor microenvironment were 25090±3820 and 10670± 1793 in the aged group and 6252±864 and 3061±451 in the young group,respectively.Moreover,the expression levels of IL-6 and IL-10(t =3.925,P =0.01;t =3.552,P =0.02)in the tumor microenvironment in the aged group were significantly lower than those in the young group.Conclusions Young mice are more susceptible to Lewis lung carcinoma,probably as a result of differences in inflammation and immunity.
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OBJECITVE: To study the inhibitive effect of plumbagin on Lewis lung cancer. METHODS: Cell proliferation was determined by CCK8 assay. Apoptosis was determined by flow cytometry. The expression of Bcl-2 and VEGF protein was studied by Western blot assay. The model of C57BL/6 mice bearing Lewis lung cancer was established by subcutaneous seeding of Lewis lung cancer cells, and randomly divided into 5 groups (n = 6). Tumor-bearing mice were injected with normal saline, plumbagin(low, medium, high dose) or cyclophosphamide (CTX) in each group. The tumor volume was measured. All mice were sacrificed on Day 22nd under aseptic condition for the tumor collection. The transplanted tumors were weighed for calculation of the tumor inhibition rate; Immunohistochemical method was applied to assessing the VEGF expression in tumor tissue. RESULTS CCK-8 assay showed that plumbagin had an obvious inhibition on Lewis lung carcinoma cells line in a dose-dependent manner(r = 0.953, P < 0.05). Plumbagin significantly increased cell apoptosis rate(P<0.05). The protein levels of Bcl-2 and VEGF were significantly reduced by plumbagin (0, 2.5, 5, 10 μmol·L-1) treatment(P < 0.05). In plumbagin(low, medium, high dose) groups and CTX group, the tumour volume, tumour weight and the expression of VEGF were significantly less than those in the control group (P < 0. 05). CONCLUSION: The plumbagin effectively inhibits Lewis lung carcinoma cells proliferation and tumor growth of Lewis lung carcinoma cells in mice. The mechanism involved is down-regulating the expression of Bcl-2, VEGF and inducing cell apoptosis.
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The incidence of lung cancer has rapidly increased and cancer patients at a later cancer stage frequently suffer from unbearable cancer-associated pain. However, the pathophysiology of lung cancer pain has not been fully described due to a lack of appropriate animal models. This study was designed to determine the effect of Lewis lung carcinoma (LLC) cell inoculation on formalin-induced pain behavior and spinal Fos expression in C57BL/6 mice. LLC cells (1.5 × 10⁵, 2.5 × 10⁵, 3.0 × 10⁵ or 5.0 × 10⁵) were inoculated into back or peri-sciatic nerve areas. Back area inoculation was adopted to determine the effect of cancer cell circulating factors and the peri-sciatic nerve area was used to evaluate the possible effects of cancer cell contacting and circulating factors on formalin-induced pain. At postinoculation day 7, LLC cell (5.0 × 10⁵) inoculations in both back and peri-sciatic nerve area significantly increased formalin-induced paw-licking time and spinal Fos expression over those in cell-media-inoculated (control) mice. Enhanced pain behavior and spinal Fos expression were significantly suppressed by ibuprofen pretreatment (250 mg/kg). The results of this study suggest that LLC cell circulating factors and inflammatory responses may be critical in enhancing pain sensation in the early stage of lung cancer cell inoculation.
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Animals , Humans , Mice , Carcinoma, Lewis Lung , Formaldehyde , Ibuprofen , Incidence , Lung Neoplasms , Models, Animal , SensationABSTRACT
Objective To investigate the effects of elemene combined with chemotherapy on S100A4 and MMP-9 protein expression in Lewis lung carcinoma mice and to explore the possible mechanism. Methods Twenty-four mice inoculated with Lewis cells were randomly divided into 4 groups,including lung carcinoma model group,chemotherapy group,elemene group,and combination group,6 mice in each group. On day 11 after inoculation, the mice in chemotherapy group were given intraperitoneal injection of etoposide (3 mg·kg-1·d-1)and cisplatin (3 mg·kg-1·d-1),the mice in elemene group were given intraperitoneal injection of elemene (100 mg·kg-1·d-1), the mice in the combination group were given intraperitoneal injection of elemene (100 mg·kg-1·d-1),etoposide (3 mg·kg-1·d-1),and cisplatin (3 mg·kg-1·d-1). After 7-day continuous treatment,the tumor body mass, spleen index, thoracic gland index, growth-inhibition rate, and metastasis-inhibition rate in various groups were measured,the contents of protein S100A4 and matrix metalloproteinase 9 (MMP-9)in tumor tissues were determined by enzyme-linked immunosorbent assay (ELISA),and the protein expression levels of S100A4 and MMP-9 were detected by immunohistochemical staining. Results In the combination group, the growth-inhibition rate and the inhibitory rate of metastases were increased obviously, the spleen index and thoracic gland index were also increased, the contents of S100A4 and MMP-9 were decreased, and the protein expression rates of S100A4 and MMP-9 were reduced(P < 0.05 or P < 0.01 compared with the chemotherapy group). Conclusion Elemene combined with chemotherapy could inhibit the Lewis lung carcinoma growth and metastasis in mice, and the possible mechanism might be associated with the decrease of S100A4 and MMP-9 protein expression in the tumor tissues.
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Objective To observe the effects of sevoflurane pretreatment on lung metastasis of mouse Lewis lung cancer (LLC)cells.Methods Mouse LLC cells were inoculated in culture plate. After being cultured for 24 h the cells were randomly divided into four groups:group control (CC), group 1% sevoflurane (SC1),group 2% sevoflurane (SC2),and group 3% sevoflurane (SC3).Cells of group SC1-3 were exposed to 1%,2%,3% sevoflurane for 4 h respectively,cells of group CC were exposed to 95%O 2-5%CO 2 mixture air,and were then cultured for another 24 h.The invasive activity of cells was determined by Transwell assay.The migration of cells was evaluated by wound scratch assay.The expression of MMP-2 and MMP-9 in cells were detected by ELISA.Thirty-two C57BL/6 mice were divided into four groups (n = 8):group control (CM),group 1% sevoflurane (SM1),group 2% sevoflurane (SM2),and group 3% sevoflurane (SM3).LLC cells of group SC1-3 were injected into caudal vein of mouse in group SM1-3 respectively.Cells of group CC were injected into mouse of group CM.Lung metastasis inhibitory rates were evaluated after 3 weeks. Results Compared with group CC,the invasive activity and migration of cells in group SC1-3 were decreased significantly,group SC1 >group SC2 >group SC3 (P group SC2>group SC3 (P <0.05).Compared with group CM,lung metastasis inhibitory rates of group SM1-3 were increased significantly,group SM1 < group SM2 < group SM3 (P < 0.05 ). Conclusion Sevoflurane can inhibit the lung metastasis of mouse LLC cells,which maybe through down-regulating the expression of MMP-2 and MMP-9 in mouse LLC cells.
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Objective: To investigate the antitumor effect of maesopsin 4-O-β-glucoside (TAT2) isolated from the leaves of Artocarpus tonkinensis (A. tonkinensis) A. Chev. ex Gagnep. Methods: The antitumor activity of TAT2 was evaluated in Lewis lung carcinoma (LLC) tumor-bearing mice. BALB/c mice had tumors induced by implantation with 2 × 10
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OBJECTIVE@#To investigate the antitumor effect of maesopsin 4-O-β-glucoside (TAT2) isolated from the leaves of Artocarpus tonkinensis (A. tonkinensis) A. Chev. ex Gagnep.@*METHODS@#The antitumor activity of TAT2 was evaluated in Lewis lung carcinoma (LLC) tumor-bearing mice. BALB/c mice had tumors induced by implantation with 2 × 10(6) LLC cells into the subcutaneous right posterior flank. Tumor-bearing mice were treated orally with a range of doses of TAT2 and a standard drug, doxorubicin. Animals were observed for tumor growth and mortality rate. Blood was collected to determine hematological and biochemical parameters.@*RESULTS@#TAT2 was isolated from an ethanolic extract of A. tonkinensis leaves. Its structure was determined by MS and NMR spectroscopy, and identified as TAT2. The compound did not show acute toxicity at the highest dose tested (2000 mg/kg body weight). TAT2 exhibited antitumor activity by decreasing tumor growth, increasing the survival rate, and ameliorating some hematological and biochemical parameters at doses of 100 and 200 mg/kg body weight (P < 0.05).@*CONCLUSIONS@#These results indicate that TAT2 possesses clear antitumor activity. Due to its bioavailability and low toxicity, and the fact that it could be isolated in a large scale from A. tonkinensis leaves, the compound shows promise as a potential anticancer drug.
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B7 homolog 1 (B7-H1) is the most potent immunoinhibitory molecule in the B7 family. In this study, we examined the effects of tumor-associated B7-H1 on T-cell proliferation in lung cancer. The expression of B7-H1 in human adenocarcinoma A549 and mouse Lewis lung carcinoma (LLC) cells were examined by flow cytometry. To assess the in vitro effect of tumor-associated B7-H1 on T-cell proliferation, we isolated T cells from peripheral blood mononuclear cells (PBMCs) of healthy individuals, labeled them with carboxyfluorescein succinimidyl ester, and co-cultured them with A549 cells in the absence or presence of anti-B7-H1 antibody. For in vivo analysis, LLC cells were subcutaneously injected into mice treated or not with anti-B7-H1 antibody. T-cell proliferation in both in vitro and in vivo assays was analyzed by flow cytometry. In vitro, co-culturing T cells with A549 cells significantly inhibited the proliferation of the former compared with the proliferation of T cells alone (P<0.01), and the addition of B7-H1 blocking antibody dramatically reversed the inhibition of T-cell proliferation by A549 cells. Similarly, in mice bearing LLC-derived xenograft tumors, in vivo administration of anti-B7-H1 antibody significantly increased the total number of spleen and tumor T cells compared to levels in control mice that did not receive anti-B7-H1 antibody. Functionally, in vivo administration of anti-B7-H1 antibody markedly reduced tumor growth. Tumor-associated B7-H1 may facilitate immune evasion by inhibiting T-cell proliferation. Targeting of this mechanism offers a promising therapy for cancer immunotherapy.
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Humans , Animals , Mice , Adenocarcinoma/pathology , B7-H1 Antigen/analysis , Cell Proliferation , Lung Neoplasms/pathology , T-Lymphocytes/pathology , A549 Cells , Antibodies, Neoplasm/therapeutic use , B7-H1 Antigen/antagonists & inhibitors , Cells, Cultured , Flow Cytometry , Immunotherapy/methods , Mice, Inbred C57BL , Neoplasms, Experimental , Splenic Neoplasms/pathology , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVE: To investigate the mechanism of inhibition and radiosensitization effects of combining treatment with tanshinone I and(irradiation) IR on mice bearing Lewis lung carcinoma(LLC). METHODS: The models of LLC in C57BL/6 mice were established via subcutaneous injection of mouse LLC cells, and divided into model control group, radiation alone group, Tan I (40 mg · kg-1) group, 5-Fu + IR group, Tan I (10, 20, 40 mg · kg-1) + IR groups. After irradiated, the relative volume of tumor was observed, the delay time of tumor growth and enhancement factor (EF) was calculated. After stripped, the inhibition rate was calculated. Cell apoptosis index( AI) was in vestigated by TUNEL staining. The protein expressions of Bcl-2 and Bax were detected by Western blot. RESULTS The different concentrations of Tan I (low, medium and high) + IR groups inhibited the tumor growth significantly, and the inhibition rate was 27.14%, 38.46%, 59.78%, respectively, which were significant difference as compared with IR group (P < 0.01). And also had the significant radiosensitizing effect, the enhancement factor was 1.09, 1.76, 2.03, respectively. The AI was 51.3% in Tan I (H) + IR group, which was significant difference as compared with IR group(P < 0.05). The expression of Bcl-2 protein was decreased, and Bax proteins was increased by combining treatment with Tan I and IR. CONCLUSION Combining treatment with Tan I and IR inhibited the tumor growth and had radiosensitizing effects in mice bearing LLC. One of the mechanism may be that it might induce apoptosis by regulated the expression of Bcl-2/Bax protein, so cells were more sensitive to radiation.
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Objective By comparing the biological characteristics among Lewis lung cancer cells ( LLC) , LLC or-thotopic transplantation derivative cells ( R1-LLC) and R1-LLC orthotopic transplantation derivative cells ( R2-LLC) , we e-valuate their invasion and metastatic abilities in orthotopic transplantation models.Methods In vitro, we applied CCK8, clonogenic assay, and Transwell invasion assay to detect the proliferation ability, invasion ability and morphologic structures of LLC,R1-LLC, R2-LLC cells respectively, meanwhile observing morphologic structures by transmission electron microsco-py.In vivo, we constructed LLC, R1-LLC and R2-LLC orthotopic transplantation models.Herein, we observed their tumor growth and metastasis.The tumor formation rate and tumor-forming time were recorded for statistic analysis.Results In vitro:LLC, R1-LLC and R2-LLC cells showed no significant difference in proliferation ability ( P>0.05 ) , but significant differ-ences in invasion ability:R2-LLC>R1-LLC>LLC(P<0.05).In vivo:In the orthotopic group, the tumor formation rates of LLC, R1-LLC and R2-LLC cells were 66.67%、80%、93.33%(P <0.05).Conclusions In orthotopic implantation mouse models, R2-LLC cells present higher invasion and metastatic ability than R2-LLC and LLC cells.
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Objective To study the effects of internal exposure of 18F-FDG (18F-2-deoxy-2-fiuoroD-glucose) on the protein expressions of P53,XIAP (X-linked inhibitors of apoptosis protein) and GADD (growth arrest and DNA damage)45 in Lewis lung carcinoma,and to explore the possibility of applying 18F-FDG as a radiotherapy drug in vivo.Methods Lewis lung cancer transplanted tumor models were established via subcutaneous injection of 0.2 ml of 2 × 107/ml Lewis lung carcinoma cells at left hind limbs of 48 C57BL/6 mice that were randomly divided into high dose group,low dose group and control group with 16 mice each.After 7 d of cancer cell inoculation,18.5 × 107 Bq and 9.25 × 107 Bq of 18F-FDG in 0.2 ml saline or equal volume of physiological saline was intraperitoneally injected into three group mice,respectively.22 d post inoculation,the protein expressions of P53,XIAP and GADD45 were immuohistochemically detected by using SP approach.Results There was significant difference among the protein expressions in each group (x2 =8.30,16.02,7.68,P ＜0.05).The mean integral optic density of protein expression increased from 0.089 ± 0.033 in control group to 0.315 ± 0.028 in high dose group for P53,and from 0.126 ± 0.023 to 0.383 ±-0.035 for GADD45,but it decreased from 0.422 ± 0.034 to 0.149 ± 0.055 for XIAP.There was significantly difference of these protein expressions in each group (P53:F=5.26,P＜0.05;XIAP:F=4.29,P ＜0.05;GADD45:F=5.98,P ＜0.05).Conclusions 18F-FDG can up-regulate the expressions of P53 and GADD45 proteins and down-regulate the expression of XIAP protein in tumor cells,and it inhibits tumor growth by promoting cell apoptosis in the Lewis lung carcinoma tissue with a P53-dependent manner.
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OBJECTIVES: Tumor-associated macrophages that generally exhibit an alternatively activated (M2) phenotype have been linked to tumor progression and metastasis. However, the role of M2-polarized macrophages in the growth and metastasis of lung adenocarcinoma remains enigmatic. The aim of this study was to explore the effect of M2 macrophages on the proliferation and migration of mouse Lewis lung carcinoma cells and tumor-induced lymphangiogenesis. METHODS: Trypan blue staining and the Transwell migration assay were performed to evaluate the effects of activated (M1 or M2) macrophages on the proliferation and migration of Lewis cells. Furthermore, vascular endothelial growth factor-C expression in Lewis cells and nitric oxide secretion from activated macrophages were detected during the co-culture assay. Following treatment with activated macrophages, lymphatic endothelial cells differentiated into capillary-like structures, and the induction of Lewis cell migration was assessed using a twodimensional Matrigel-based assay. RESULTS: In the co-culture Transwell system, the proliferation and migration of Lewis cells were promoted by M2 macrophages. Moreover, the co-culture significantly increased the expression of vascular endothelial growth factor-C by Lewis cells and reduced the secretion of nitric oxide from M2 macrophages, which subsequently led to the capillary morphogenesis of lymphatic endothelial cells. Interestingly, following co-culture with Lewis cells, the function of RAW264.7 cells was polarized toward that of the M2 macrophage phenotype. CONCLUSION: M2-polarized macrophages promoted the metastatic behavior of Lewis cells by inducing vascular endothelial growth factor-C expression. Thus, the interruption of signaling between M2 macrophages and Lewis cells may be considered to be a new therapeutic strategy.
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Animals , Mice , Carcinoma, Lewis Lung/secondary , Lung Neoplasms/pathology , Macrophages/physiology , Vascular Endothelial Growth Factor C/metabolism , Cell Line, Tumor , Cell Migration Assays , Cell Movement , Cell Proliferation , Carcinoma, Lewis Lung/metabolism , Endothelial Cells/pathology , Lung Neoplasms/metabolism , Lymphangiogenesis/physiology , Macrophages/cytology , Time Factors , Vascular Endothelial Growth Factor C/physiologyABSTRACT
Objective To study the effects of umbilical cord-derived mesenchymal stem cells (MSCs) on the growth and metastasis of lung cancer using Lewis lung carcinoma animal models. Methods Animal models of Lewis lung carcinoma were established in 16 C57BL/6 mice and were randomly divided into normal saline (NS) group and MSC group (n = 8). Mice in the MSC group were injected with 1×106 MSCs via the tail vein at day 7, 12, and 17. All mice were sacrificed to observe the lung metastases and the tumor size at day 21. Results The average tumor weight was (4. 587 5 ± 1. 04) g in the NS group and (4. 155 ± 1. 13) g in the MSC group (P = 0. 59). The average number of lung metastasis nodules was 3. 75 ± 1. 39 in the NS group and 1. 13 ± 1. 13 in the MSC group (P<0. 01), showing an inhibitory rate of 70%. Conclusion Umbili cal cord-derived MSCs have no effects on the growth of Lewis lung carcinoma in mice, but they can inhibit tumor metastasis.
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Objective To observe the effects of CEJS combined with chemotherapy on the expression of VEGF in lewis lung carcinoma.Methods Tumor xenografts models were set up and randomly divided into five groups including control group,CTX CEJS,high-dose CEJS joint CTX(combination group 1),and middle-dose CEJS joint CTX(combination group 2).Paraffin imbedding and HE staining were performed,and the tissue Shape was observed by microscope after section.The expressions of VEGF in five groups were determined by immuno-histochemistry.Results The expression level of VEGF could be significantly down-regulated in CTX or combination group 1 and 2,compared with the control group(P＜0.05):CEJS group had no significant difference to the control group(P＞0.05);The average optical density in the combination group 1 and 2 showed no significantly difference to the CTX group(P＞0.05).Conclusion The inhibition of CEJS could not down regulate of the expression of VEGF,but CEJS could keep the affection of chemotherapy drugs on VEGF.
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Objective To investigate the effect of Kanglaite injection (KLT) on immunological function of rat models with Lewis lung carcinoma. Methods Forty C57BL/6 mice were used to establish Lewis lung carcinoma models and divided randomly into the high dose(25 mL/kg), middle dose (12.5 mL/kg) and low dose (6.25 mL/kg) of KLT groups and model group(n=10). The mice in the KLT groups were sacrificed after injecting corresponding dose of KLT with intraperitoneal injection for 14 d. No treatment was performed on the rats in model group. The body weight, tumor and spleen weight was weighed, then the ratio of tumor restriction and the index of spleen was calculated. MTT colorimetric method and ELISA were used to detected activity of T cell proliferation and expression of IL-2 in spleen. The expression of NF-κB and IκBα protein was detected by Western blot. Results The ratio of tumor restriction in the high, middle, low dose of KLT groups decreased gradually. The indexes of spleen of the high and middle dose of KLT groups were higher than those in the model group (P<0.05 or P<0.01).Compared with the model group, the activity of T cell proliferation in the high, middle, low dose of KLT groups and the expression of IL-2 in the high and middle dose of KLT groups was increased significantly (P<0.05 or P<0.01). The expression of NF-κB protein in the nuclei of high, middle, low dose of KLT groups increased dose-dependently, and the expression of NF-κB and IκBα protein in the cytoplasm decreased dose-dependently. ConclusionKLT could enhance immunological function by effecting T cell proliferation, expression of IL-2, NF-κB and IκBα, while restricting tumor growth in Lewis lung carcinoma models.
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Objective To observe HA14-1 sensitizes Lewis lung carcinoma in mice to cyclophosphamide (CTX) and to explore its possible mechanism. Methods Forty Lewis lung carcinoma model mice were randomly divided into 4 groups:normal saline group,CTX group, HA14-1 group,CTX+HA14-1 group. After the treatment of 7 days,all of the mice were killed on the 22nd day of tumor inoculation. The tumor volume growth curve of each group was described;tumor inhibition rate was caculatued;Bcl-2,Bax,Caspase-9 protein expression levels before and after the treatment were determined by immunohistnehemistry. Results Compared to the normal saline group,HA14-1 group had no significant effect on inhibiting tumor volume,and the tumor volume in HA14-1 group increased less slowly than that of CTX group, HA14-1 group and CTX+HA14-1 group. Compared to the normal saline group, the tumor inhibition rate of HA14-1 group had no significant increase (P> 0.05),while that of CTX group and CTX + HA14-1 group increased significantly (P< 0.05);compared to the CTX group,the tumor inhibition rate of CTX + HA14-1 group increased significantly (P < 0.05). Bcl-2 protein expression levels in CTX group,HA14-1 group and CTX+HA14-1 group were lower than that in the normal saline groups compared to CTX group,Bcl-2 protein expression of CTX + HA14-1 group reduced significantly. Compared to the normal saline group,the expression levels of Bax and Caspase-9 protein in CTX group, HA14-1 group and CTX+HA14-1 group increased significantly (P< 0.05);compared to CTX group,CTX + HA14-1 group increased more significantly (P < 0.05). Conclusion HA14-1 might enhance the efficiency of CTX chemotherapy via inhibiting the expression of Bcl-2, increasing the expression of Bax and caspase-9 and promoting tumor cell apoptosis.
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Objective To investigate the inhibitory effects of CIK on the proliferation of Lewis lung carcinoma cell line and the growth of transplanted Lewis lung carcinoma in C57BL/6N mice in vivo.Methods CIK cells were induced by culturing PBMC with regular method.The proliferation of Lewis lung carcinoma cells was measured by MTT assay.Uhramicrostrueture of Lewis lung carcinoma cells was observed under a transmission electron microscope.Flowcytometric analysis was used to detect cell apoptosis.Ultrastructural observation expressions of FasL were individually determined by MTT and immunocytochemistry(ICC) analysis.Results Electron microscopic observations sbowed that CIK cells could induce the hepatoma cells to apoptosis.Flow cytometric analysis demonstrated that apoptosis cells of Lewis lung carcinoma were increased in CIK group compared with those in the control group.FasL expression on CIK increased.Cytotoxieity was blocked after addition of anti-FasmAb.Conclusion CIK has inhibitory effect on Lewis lung carcinoma cells both in vitro and in vivo.CIK cells can induce the apoptosis of Lewis lung carcinoraa cells.and Fas/FasL pathway plays an important role in apoptosis of Lewis lung carcinoma cells by CIK.
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Toxoplasma gondii is an obligate intracellular protozoan parasite that induces antitumor activity against certain types of cancers. However, little information is available regarding the immunologic mechanisms that regulate these effects. For this purpose, C57BL/6 mice were administered either the T. gondii Me49 strain orally or Lewis lung carcinoma (LLC) cells intramuscularly. Survival rates, tumor size, histopathology, and immune responses were determined for each group, and angiogenesis was evaluated by in vivo Matrigel plug assay. Toxoplasma-infected (TG-injected) mice survived the entire experimental period, whereas cancer cell-bearing (LLC-injected) mice died within six weeks. Mice injected with both T. gondii and cancer cells (TG/LLC-injected group) showed significantly increased survival rates, CD8+ T-cell percentages, IFN-gamma mRNA expression levels, serum IgG2a titers, and CTL responses as compared to the LLC-injected mice. In addition, angiogenesis in the TG/LLC-injected mice was notably inhibited. These effects in TG/LCC-injected mice were similar or were increased by the addition of an adjuvant, Quil-A. However, TG/LLC-injected mice showed decreased percentages of CD4+ and CD8+ T cells, IFN-gamma mRNA expression levels, and serum IgG1 and IgG2a titers as compared to TG-injected mice. Taken together, our results demonstrate that T. gondii infection inhibits tumor growth in the Lewis lung carcinoma mouse model through the induction of Th1 immune responses and antiangiogenic activity.
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Animals , Female , Mice , Base Sequence , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Carcinoma, Lewis Lung/blood supply , Cell Line, Tumor , Cytotoxicity, Immunologic , DNA Primers/genetics , Immunoglobulin G/blood , Immunotherapy/methods , Interferon-gamma/genetics , Mice, Inbred C57BL , Neovascularization, Pathologic , RNA, Messenger/genetics , Th1 Cells/immunology , Toxoplasma/immunologyABSTRACT
Objective To observe the effect of antitumor and hematopoiesis of the extract of Spatholobus suberctus Dunn (SSCE) in vivo. Methods The mouse model of Lewis lung carcinoma was used to investigate the effects of SSCE on tumor growth and hematopoiesis by detecting the counts of peripheral blood, the counts and classify of the cells in bone marrow. Result The tumor inhibitory rate of SSCE on Lewis lung cancer was 30.65%. SSCE can stimulate the proliferation of bone marrow cells and relieve the marrow depression induced by chemotherapy, at the same time, the physique of the mouse treated by SSCE was not effected. Conclusion SSCE exits antitumor effect, moreover, it can stimulate the bone marrow cells to proliferate and relieve the marrow depression produced by chemotherapy.
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PURPOSE: Photodynamic therapy was used to lung cancer. We have made a light microscpic study on the effects of photodynamic therapy to tumor graft in skin of mice, when the power density was 600 mW/cm2 with reducing time. MATERIALS AND METHODS: These studies had been performed on sixteen C57BL/6 mice that Lewis lung carcinoma cells had been implanted. All mice were divided into four groups. One of four groups received Photogem 3 mg/kg intravenously 24 hours prior to exposure of tumor to 180 J/cm2 laser light vertically at a wavelength 635etam with a higher power density of 600 mW/cm2 than that of 400 mW/cm2 clinically. One of these group received only Photogem. The others not received Photogem and one of these irradiated with laser. The light source was the wavelength of 635 etam Diode Laser (Laxcell 2004, Bio- Optics. co. Korea) After photodynamic therapy was finished, staining and analysing of tumors were used to determine the natures and extents of injury. RESULTS: Grossly response was not observed. Histologically, there were loss of endothelium from small vessel at tumor and muscle with thrombus formation. There were focal necrosis with infiltration of inflammatory cells at tumor and adjacent tissues that irradiated with laser, regardless of administration of Photogem. CONCLUSION: Photodynamic therapy using Photogem and LASER with power density of 600 mW/cm2 destroy not only tumors incompletely but also adjacent normal tissue.