Chronic psychological stress aggravates intestinal barrier damage and promotes enteritis development through inhibiting Wnt/β-catenin pathway / 中华微生物学和免疫学杂志

Objective:To investigate the mechanism by which chronic psychological stress aggravates intestinal barrier damage and promotes the development of enteritis through inhibiting Wnt/β-catenin pathway, so as to provide a new therapeutic strategy for the clinical diagnosis and treatment of inflammatory bowel disease (IBD).Methods:A comorbidity model of chronic psychological stress and enteritis was established using C57BL/6J mice. HE staining was used to analyze the effects of chronic psychological stress on the intestinal pathological damage in mice with enteritis. ELISA was used to detect the expression of proinflammatory cytokines. The ultrastructural changes of colonic cells and the state of intestinal mucus layer were observed under transmission electron microscope and scanning electron microscope. The secretion of mucoprotein 2 (MUC2) and the expression of cell proliferation marker Ki67 were detected by immunofluo rescence staining. The numbers of goblet cells were detected by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Western blot was performed to analyze the expression of tight junction protein between intestinal epithelial cells, β-catenin which was a key protein of Wnt/β-catenin pathway maintaining crypt proliferation, and downstream protein c-myc.Results:The sugar water consumption ratio decreased, but tail suspension immobility time, the swimming immobility time and the expression of corticotropin releasing hormone (CRH) in hypothalamus increased (all P<0.05) in the stress group as compared with those in the control group. Chronic psychological stress promoted weight loss and colonic shortening in mice with enteritis, exacerbated pathological damage and enhanced the release of pro-inflammatory factors. Moreover, increased disappearance of intestinal epithelial microvilli and severe cellular ultrastructural damage were also observed in the stress+ dextran sulfate sodium salt (DSS) group. There was no pathological damage in the control and stress groups. Chronic psychological stress aggravated intestinal barrier injury and inhibited intestinal barrier repair by inhibiting Wnt/β-catenin pathway. Conclusions:In the mouse model of DSS-induced enteritis, chronic psychological stress preconditioning inhibited the Wnt/β-catenin pathway, weakened the repair ability of intestinal epithelium, aggravated the loss of mucus layer of intestinal barrier and the damage of tight junction structure, and promoted the development of enteritis. In the absence of enteritis, chronic psychological stress had no significant effects on the Wnt/β-catenin pathway and the intestinal barrier.

Expression of cold-inducible RNA-binding protein in radiation-induced lung injury model / 中国辐射卫生

Objective To investigate the changes in the expression of cold-inducible RNA-binding protein (CIRBP) in a radiation-induced lung injury model. Methods Thirty male C57BL/6 mice were randomly divided by body weight into control group (no intervention) and model group (single chest X-ray irradiation with a dose of 20 Gy to build a radiation-induced lung injury model). The mice were dissected five weeks after irradiation. Hematoxylin-eosin staining and Masson staining were used to observe the pathological changes of the lung tissue and the deposition of collagen fibers. Immunohistochemistry was used to measure the expression of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the lung tissue. qRT-PCR was used to measure the expression of CIRBP mRNA in the lung tissue. The expression of CIRBP protein in the lung tissue was determined by the immunofluorescence assay and Western blot. Results Compared with the control group, the model group showed significant pulmonary vascular congestion, significant inflammatory cell infiltration, significant thickening of some alveolar septa, significantly increased IL-6 expression [(129.41 ± 5.58) vs (187.22 ± 34.77), t = 3.179, P < 0.05], significantly increased TNF-α expression [(137.52 ± 23.53) vs (187.02 ± 19.16), t = 5.069, P < 0.05], significantly increased CIRBP mRNA expression [(1 ± 0.08) vs (1.97 ± 0.39), t = 3.45, P < 0.05], and significantly increased CIRBP protein expression [(9.32 ± 1.26) vs (14.76 ± 1.61), t = 3.751, P < 0.05], by the immunofluorescence assay; [(1.13 ± 0.17) vs (1.49 ± 0.14), t = 2.819, P < 0.05], by Western blot). Conclusion The expression of CIRBP is significantly increased in the radiation-induced lung injury model, which may be an important pro-inflammatory factor in radiation-induced lung injury.

Study on biological behavior of small tumor breast cancer with axillary lymph node metastasis as the first symptom / 中国医师进修杂志

Objective:To explore the biological behavior of small tumor (≤1.0 cm) breast cancer with axillary lymph node metastasis as the first symptom, and to provide a powerful reference for clinical accurate treatment.Methods:The clinical, pathological and follow-up data of 60 breast cancer patients with small tumor and axillary lymph node metastasis as the first symptom admitted to the Second Affiliated Hospital of Harbin Medical University and the Third Affiliated Hospital of Harbin Medical University from 2017 to 2019 were analyzed retrospectively (study group). Meanwhile, non-small tumor with negative lymph node (control group A), non-small tumor with positive lymph node (control group B) and small tumor with negative lymph node (control group C) were included as control groups. Selected estrogen receptor(ER), progesterone receptor(PR), human epidermal growth factor receptor-2(Her-2) and Ki67 to compare and analyze the difference between primary lesions and axillary lymph node metastasis, and made a comprehensive analysis with the follow-up data.Results:There were no statistically significant differences in the four indexes in primary lymph nodes and metastatic lymph nodes between the study group and the control group ( P>0.05). The expression of HER-2 in control group B, study group, control group C, control group A showed a decreasing trend. In the study group, there were 19 cases with >3 axillary lymph node metastasis, the positive rate of HER-2 was 11/19, and 37 cases with 3 lymph node metastasis, the positive rate of HER-2 was 21.6%(8/37), the difference was statistically significant ( P<0.05), but there was no significant difference in the expression of ER, PR and Ki67 ( P>0.05). In control group B, there was no significant difference between the groups with >3 axillary lymph node metastasis and 3 groups ( P>0.05). Combined with the follow-up data, in the study group with >3 lymph node metastasis, there were 4 cases with distant metastasis and Ki67 expression rate was 4/4, while there were 13 cases with no distant metastasis and Ki67 expression rate was 5/13, the difference was statistically significant ( P<0.05). Conclusions:The expressions of ER, PR, Her-2 and Ki67 in primary breast cancer including small tumor and axillary lymph node metastasis are consistent. In most cases, the overall condition can be evaluated by biological indicators of primary disease, but some patients do have inconsistencies, which should arouse the attention of clinicians for comprehensive condition evaluation. Her-2 positive expression seems to be related to axillary lymph node metastasis as a whole, especially in small tumor breast cancer with T≤1.0 cm. For patients with axillary lymph node metastasis and invasive ductal carcinoma with primary lesion ≤1.0 cm, the high expression of Ki67 seems to indicate that distant metastasis is more likely to occur in the longer term.

Effect of targeted silencing Notch1 on proliferation and apoptosis of human non-small cell lung cancer stem cells / 国际肿瘤学杂志

Objective To investigate the effect of targeted silencing Notch1 on proliferation and apoptosis of human non-small cell lung cancer stem cells.Methods Lung cancer A549 cells and SPC-A-1 cells were selected and divided into control group,Nc-shRNA group and Notch1-shRNA group.The Nc-shRNA group was a negative control RNAi lentivirus group,and the Notch1-shRNA group was a Notch1 inhibitory RNAi lentivirus group.The lentiviral-mediated shRNA interference technology was used to target the silencing of Notch1.The silencing effect of Notch1 gene was verified by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting.Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) and sarcosphere formation assay.Apoptosis was detected by Annexin V/7-AAD double staining.Western blotting was used to detect the expression of proliferating cell nuclear antigen (PCNA),B-cell lymphoma-2 (Bcl-2) and Notch1 downstream gene Hes-1.Results The results of qRT-PCR showed that the relative expression levels of Notch1 in control group,Nc-shRNA group and Notch1-shRNA group in A549 cells and SPC-A-1 cells were 1.000 ± 0.000,0.937 ± 0.025,0.490 ± 0.036 and 1.000 ± 0.000,1.077 ± 0.070,0.373± 0.038,with statistically significant differences (F =359.707,P ＜0.001;F =210.455,P ＜0.001),further paired comparison,the relative expression of Notch1 in Notch1-shRNA group was significantly lower than that in Nc-shRNA group (all P ＜ 0.05).Western blotting showed that the expressions of Notch1 protein in A549 cells and SPC-A-1 cells were consistent with the mRNA results.MTT assay showed that the 24 h A values of A549 cells in control group,Nc-shRNA group and Notch1-shRNA group were 0.209 ± 0.005,0.219 ± 0.009,0.159 ±0.006,48 h A values were 0.293 ± 0.004,0.302 ± 0.004,0.205 ± 0.005,72 h A values were 0.450 ± 0.003,0.430 ± 0.012,0.348 ± 0.017,with statistically significant differences (F =79.487,P＜0.001;F =508.664,P ＜0.001;F =57.156,P ＜0.001),further paired comparison,the proliferation ability of Notch1-shRNA group was significantly lower than that of Nc-shRNA group at 24,48,72 h (all P ＜ 0.05).The 48 h A values of SPC-A-1 cells in control group,Nc-shRNA group and Notch1-shRNA group were 0.438 ±0.022,0.412 ± 0.015,0.364 ± 0.010,72h A values were 0.540 ± 0.016,0.519 ± 0.009,0.438 ± 0.019,with statistically significant differences (F =15.667,P =0.004;F =37.299,P ＜ 0.001),further paired comparison,the proliferation ability of Notch1-shRNA group was significantly lower than that of Nc-shRNA group at 48 h and 72 h (all P ＜ 0.05).The sphere sizes of control group,Nc-shRNA group and Notch1-shRNA group in A549 cells were (149.667 ± 6.506) μm,(136.667 ± 7.095) μm,(86.676 ± 7.638) μm,with statistically significant difference (F =65.940,P ＜ 0.001).The sphere sizes of the three groups in SPC-A-1 cells were (118.667 ± 6.658) μm,(128.000 ± 7.000) μm,(60.675 ± 4.509) μm,with statistically significant difference (F =105.372,P ＜0.001).Further paired comparison,the sphere size of Notch1shRNA group was significandy smaller than that of Nc-shRNA group in the two kinds of cells (all P ＜ 0.05).The apoptosis rates of control group,Nc-shRNA group and Notch1-shRNA group in A549 cells and SPC-A-1cells were (0.489 ± 0.014)％,(0.633 ± 0.021)％,(1.683 ± 0.221)％ and (1.323 ± 0.194)％,(1.690 ± 0.188) ％,(3.017 ± 0.356) ％,with statistically significant differences (F =77.660,P ＜ 0.001;F=32.200,P =0.001),further paired comparison,the apoptosis rate of Notch1-shRNA group was significantly higher than that of Nc-shRNA group in the two kinds of cells (all P ＜ 0.05).Western blotting showed that the expressions of PCNA,Bcl-2 and Hes-1 in control group,Nc-shRNA group and Notch1-shRNA group in A549 cells were statistically significant (F =155.343,P ＜ 0.001;F =22.576,P =0.002;F =70.108,P＜0.001),and the expressions of PCNA,Bcl-2 and Hes-1 in the three groups in SPC-A-1 cells were statistically significant (F =49.419,P ＜0.001;F =28.090,P =0.001;F =12.040,P =0.007).Further paired comparison,the expressions of PCNA,Bcl-2 and Hes-1 in Notch1-shRNA group were significantly lower than those in Nc-shRNA group in the two kinds of cells,and the differences were statistically significant (all P ＜0.05).Conclusion Targeted silencing of Notch1 can reduce the proliferation activity of lung cancer stem cells and promote apoptosis,which may be related to the down-regulation of its downstream gene Hes-1.

Regulatory mechanism of PESV on tumor-infiltrating natural killer cells in liver orthotopic transplantation tumor / 中国免疫学杂志

Objective:To investigate the regulatory mechanism of PESV on tumor-infiltrating natural killer ( NK) cells in a mice model with H22 orthotopic transplantation tumor .Methods:Suspensions of H22 cells were injected into the lobe of liver on C 57BL/6 mice for establishing liver orthotopic transplantation tumor model ,then the mice were randomly divided into four groups:normal group , control group ,PESV low dose group ( PESV-L ) and PESV high dose group ( PESV-H ) .Mice were either sacrificed for mechanistic studies or survival followed 14 days of therapy.The volume and weight of the tumor were measured .The proportion of infiltrating NK cells was measured by flow cytometry and the expression of NK 1.1(NK) cells was investigated by immunohistochemistry method .The expression of perforin and granzyme B were further investigated by real-time PCR.Results: In contrast to control group , the tumor inhibition rate was 15.38%and 30.77% in PESV-L group and PESV-H group respectively.The survival showed that PESV-H could significantly prolong the survival time of mice ,and life extension rate was 34.06%,(P<0.05).Histological analysis revealed significant pleomorphism of the neoplastic cells and invasive extendion in control group ,while there were more necrosis and less degree of atypia in PESV-L and PESV-H.The level of tumor-infiltrating NK cell was significantly higher in PESV-H than in tumor-bearing control group [(5.91±0.49)%vs.(3.69±0.50)%,P<0.05],and NK cells were infiltrating in peritumoral lesions.The mRNA of perforin and granzyme B in PESV-H were respectively 3.62 and 5.82 times than that of control group ( P<0.05 ) .Conclusion: These findings suggest that the treatment of PESV might increase the infiltration of natural killer cells in the orthotopic transplantation tumor and contribute to NK cells migration to the tumor , which induct and maintain the activities of natural killer cells against tumor cells by expressing perforin and granzyme B in vivo .

Analysis of serum insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in patients with impaired glucose regulation and benign prostate hypertrophy / 实用医学杂志

Objective To study the relationship between IGF-1, IGFBP-3 and prostatic volume (PV) by examining the levels of insulin and insulin-like growth fator-1 (IGF-1) and insulin-like growth factor binding protein-3 ( IGFBP-3 ) and other indicators in patients with impaired glucose regulation and benign prostate hypertrophy. Methods According to 75 g oral glucose tolerance test (OGTT) results, 109 BPH patients aged over 50 years were divided into three groups: normal glucose tolerance (NGT) group (n = 56), impaired fasting glucose (IFG) group (n = 14), impaired glucose tolerance (IGT group, n = 39). The biochemical indicators and postatic hyperplasia related factors and IGF-1, GFBP-3 were measured. Results There were no statistical differences between the three groups in terms of blood lipids, homocysteine, urinary inhibition C, fasting insulin (FINS), glycosylated hemoglobin, IGF-1 and IGFBP-3 (P > 0.05). There were no significant differences between the groups in terms of PV, prostate specific antigen, the quality of life score and the international prostate symptom score (P > 0.05). Fasting plasma glucose and insulin resistance index (HOMA IR) were higher in IFG group than NGT group (P′ < 0.017) and IGT group (P′ < 0.017). 2-hour plasma glucose and 2-hour insulin were higher in IGT group than NGT group (P′ < 0.017) and IFG group (P′ < 0.017). PV was positively correlated with FINS but not correlated with IGF-1, IGFBP- 3 by multiple multiple step wise regression analysis. Conclusion Oyperinsulinemia is a risk factor in the development of BPH with IGR, and IGF-1 and IGFBP-3 are not associated with BPH risk. Further investigation is needed to elucidate the role of the IGF-1 and IGFBP-3 in BPH.

Sorafenib inhibits tumor growth through modulating vasculogenic mimicry in a hepatocellular carci-noma xenograft model / 国际肿瘤学杂志

Objective To investigate the effects and the mechanism of sorafenib on hepatocellular car-cinoma growth and vasculogenic mimicry (VM)in mice.Methods A subcutaneous implantation mouse model of human hepatocellular carcinoma (HCC)HepG2 cells were established.Mice inoculated with HepG2 cells were randomly divided into the treatment group (sorafenib 30 mg·kg -1 ·d -1 )and the control group by using of paired comparison method.Growth of established tumor xenografts was monitored at least twice weekly by vernier caliper measurements.VMwas assessed by immunohistochemical assay and periodic acid schiff reaction (PAS)histochemical double-staining.The expressions of HIF-1 α,VEGFA,VEGFR-1 and MMP-2 in tumor tissues were also assessed by immunohistochemical assay,Western blotting and real-time quantitative PCR. Results The tumor volume in the sorafenib group was obviously decreased compared with the control group (809.69 mm3 ±208.71 mm3 vs 1 678.00 mm3 ±31 3.29 mm3 ),with a statistically significant difference (t =6.1 03,P =0.030).Haematoxylin and eosin (HE)staining showed that tumor tissues treated with sorafenib were characterized by obvious necrosis,but there were not the same cases in the control group.Sorafenib group significantly reduced the number of tumor functional vessel in HepG2 xenografts compared with the control group,as assessed by tumor vasculature uptake of DiOC7 (4.77 ±0.1 5 vs 8.44 ±0.68,t =9.1 92,P =0.01 3).The number of VMwas significantly decreased by sorafenib (1 .04 ±0.46 vs 2.66 ±0.42,t =4.51 0, P =0.041 ).Relative to controls,CD31 -positive vessels decreased after treatments (3.42 ±0.1 0 vs 1 .26 ± 0.1 4),with a statistically significant difference (t =21 .580,P =0.002).Compared with the control group, the protein levels of HIF-1 α(0.65 ±0.03 vs 1 .00 ±0.00),VEGFA (0.51 ±0.02 vs 1 .00 ±0.00), VEGFR-1 (0.45 ±0.04 vs 1 .00 ±0.00)and MMP-2 (0.69 ±0.02 vs 1 .00 ±0.00)were significantly decreased in the sorafenib group (t =1 9.650,P =0.003;t =40.493,P =0.000;t =23.429,P =0.002;t =26.071 ,P =0.002).Compared with the control group,the mRNA levels of HIF-1 α(0.78 ±0.05 vs 1 .00 ±0.00),VEGFA (0.52 ±0.05 vs 1 .00 ±0.00),VEGFR-1 (0.45 ±0.02 vs 1 .00 ±0.00)and MMP-2 (0.71 ±0.02 vs 1 .00 ±0.00)were also significantly decreased in sorafenib group (t =6.840,P =0.021 ;t =27.71 0,P =0.001 ;t =62.740,P =0.000;t =23.850,P =0.002).Conclusion Sorafenib can inhibit the tumor growth and VMchannels formation,which may be related with the HIF-1 αand VEGFA /VEGFR-1 signa-ling pathway.

Mechanisms for inhibition effects of polypeptide extract from scorpion venom (PESV) on proliferation of A549 cell lines in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the mechanisms for inhibition effects of PESV on proliferation of non-small cell lung cancer cell line A549.</p><p><b>METHOD</b>MTT was used to observe cell growth and proliferation of A549 at different concentrations of PESV. Flow cytometry (FCM) was applied to analyze cell cycle distribution. Immunocytochemistry and western blot assay was recruited to detect the expression of VEGF, HIF-1alpha, PTEN after the intervention of PESV.</p><p><b>RESULT</b>A549 cells may be arrested mainly in G0/G1 phase and cell proliferation was significantly inhibited (P < 0.01) after PESV intervention in a certain range of concentration. PESV can significantly reduce the expression of HIF-1alpha,VEGF and increase the expression of PTEN.</p><p><b>CONCLUSION</b>PESV can block cell cycle and inhibit angiogenesis directly to inhibit cell proliferation of non-small cell lung cancer cell line A549 mainly through reducing the expression of HIF-1alpha, VEGF and increasing the expression of PTEN.</p>

Effect of polypeptide extract from scorpion venom (PESV) with chemotherapy inhibited angiogenesis of Lewis lung carcinomas / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of polypeptide extract from scorpion venom (PESV) alliance with chemotherapy on angiogenesis of Lewis lung carcinomas (LLC) and its mechanism.</p><p><b>METHOD</b>LLC 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.</p><p><b>RESULT</b>The 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).</p><p><b>CONCLUSION</b>PESV 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.</p>

Effect of polypeptide extract from scorpion venom (PESV) on expression of HIF-1alpha and SDF-1/CXCR4 in repopulating H22 tumour tissue during chemotherapy treatment / 中国中药杂志

<p><b>OBJECTIVE</b>To study the expression of HIF-1alpha and SDF-1/CXCR4 in repopulating H22 tumor tissue and the mechanism of angiogenesis of polypeptide extract from scorpion venom (PESV) during chemotherapy treatment.</p><p><b>METHOD</b>The expression of HIF-1alpha and SDF-1/CXCR4 in H22 tumor tissue was monitored by immunohistochemistry, and the expression level was determined by Qwin V3 image analyzing software. The correlation between HIF-1alpha and SDF-1 was analyzed. SDF-1 content was detected by ELISA.</p><p><b>RESULT</b>HIF-1alpha expression was found no difference in model group between 14 d and 21 d, and up-regulated in 28 d. There was no change of HIF-1alpha expression was observed in low-dose PESV group. In high-dose PESV group, the level of HIF-1alpha expression was high in 14 d and low in 21 d. ELISA detecting showed SDF-1 content increased slowly from 14 d to 21 d, highly from 21 d to 28 d. But in high-dose PESV groups, the content increased slowly all the time. The immunohitochemistry method got the same result with ELISA. Correlation analysis showed r = 0.805. CXCR4 expression down-regulated in two PESV treated groups, and no difference was found between these two groups.</p><p><b>CONCLUSION</b>HIF-1alpha and SDF-1 participated in VEGF expression and angiogenesis in tumor tissue during chemotherapy, while PESV could inhibit the expression of HIF-1alpha and SDF-I.</p>

Inhibitive effect of polypeptide extract from scorpion venom on repopulation in H22 tumor cell during chemotherapy / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the inhabitive effect and mechanism of polypeptide extract from scorpion venom (PESV) on repopulation in H22 tumor cell during chemotherapy.</p><p><b>METHOD</b>H22 tumor cells were injected into 96 mice subcutaneously, then mice were divided into 4 groups radomly: Model, low-dose-PESV, high-dose-PESV, and control. Reppulation model was established by 5-Fu treating mice with H22. Four groups was treated differently, 6 mice of each group was sacrificed every 7 days, measured tumor volume twice one week. The expression of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), CD105 microvessel density (CD105-MVD) and platelet derived growth factor (PDGF) in H22 tumor issue was observed by using immunohistochemistry and grey analysis, the relation of VEGF and MVD was affirmed by correlation analysis.</p><p><b>RESULT</b>In control group tumor volume of H22 increased quickly in 13-24 day, and all mice died before 27 day. In model tumor volume increased quickly before 17, in 17-22 day slowly, after 22 day quickly again, and all the mice died before 31 day. In low and high dose PESV, tumor volume added slowly, and only in 17 day there was significant difference between these two groups. Immunohistochemistry showed, PCNA expression of model group in 31 day was higher than in 21, 28 day, the expression level of high and low PESV group was lower than model group all the time, only in 17 day there was significant difference between high and low PESV group. Immunohistochemitry showed, compared with high and low dose PESV group, CD105-MVD of model group was higher in 21, 28 day (P < 0.05) and in 35 day (P < 0.01), and no difference was found between high and low dose PESV. VEGF expression of model group in 35 day was higher than in 21, 28 day (P < 0.01), and model group higher than high and low dose PESV in 21, 28, 35 day. The expression of PDGF in model decreased gradually, in high and low dose PESV, the expression was lowest in 21 day. In day 35 high dose PESV higher than low dose PESV. There was positive correlation (r = 0.669) between VEGF expression and CD105-MVD.</p><p><b>CONCLUSION</b>PESV can inhabit repopulation of H22 tumor cell during chemotherapy, and the mechanism maybe is through anti-angiogenesis and nomalizing tumor vessels.</p>

Effect of polypeptide extract from scorpion venom (PESV) on immune escape of Lewis lung carcinomas / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of polypeptide extract from scorpion venom (PESV) on immune escape of Lewis lung carcinomas (LLC) and its mechanism.</p><p><b>METHOD</b>Forty C57BL/6J mice were inoculated with LLC cells suspension (1 x 10(7) cells/ mL) in right armpit subcutaneously. The tumor-bearing mice were randomly divided into two groups: the control group and the PESV group. PESV was intragastrically subjected to the mice of the experimental group for 18 days. The tumor volume and tumor inhibitory rate were determined. The expression levels of VEGF,TGF-beta1 and IL-10 in tumor microenvironment were determined by immunohisto-chemistry-staining and ELISA. Surface co-stimulatory molecules CD80 and CD86 of tumor infiltrating dendritic cells (DC) were determined by immunohistochemistry-staining and flow cytometry.</p><p><b>RESULT</b>The growth inhibitory rate of PESV was 56. 60%. The expression levels of VEGF,TGF-beta1 and IL-10 were decreased in tumor and serum, while the expression of co-stimulatory molecules CD80 and CD86 on DC were increased in tumor. Compared with the control group, the differences were all significant (P < 6.05).</p><p><b>CONCLUSION</b>PESV was effective in recovering immuno-surveillance and intervening immune escape of lung cancer through multi-pathway. And its effects might be attained by decreasing the level of VEGF, TGF-beta1 and IL-10 in tumor microenvironment and increasing the expression of co-stimulatory molecules CD80 and CD86 on DC.</p>