| Th17 cells and IL-17 factor play an important role in angiogenesis in gastric cancer,liver cancer,breast cancer,ovarian cancer and so on.IL-17 A can act on a variety of cells and induce secretion of various growth factors,angiogenic factors,angiogenic chemokines and matrix metalloproteinases,involved in inflammatory response and angiogenesis.However,the effect of IL-17 on the growth,metastasis and angiogenesis of lung cancer is still unclear.Therefore,the role of IL-17 in the angiogenesis of lung cancer is studied and the mechanism is discussed.First,we collected 53 cases of NSCLC specimens,analyzed the positive expression of IL-17 and MVD correlation;followed by a separate application of IL-17 neutralizing antibody and its combination of DC101(anti-VEGFR antibody)treatment of lung cancer orthotopic transplant tumor model and the tumor growth and metastasis were monitored by small animal live imaging.After the mice were sacrificed,the microvessel density was measured by immunohistochemistry.The expression of IL-17 and VEGF in peripheral blood of mice was further detected by ELISA and the percentage of TH17 cells and Treg cells in the spleen of mice were detected by flow cytometry.The role of IL-17 in angiogenesis of non-small cell lung cancer and its related mechanism were investigated by the above experimental study.1 Expression of IL-17 in NSCLC and its correlation with tumor angiogenesis53 cases of NSCLC surgical resection were collected,The results of immunohistochemistry showed that there were 34 cases of IL-17 positive expression and 19 cases of negative expression.The expression of IL-17 was not related to the sex,lymph node metastasis and differentiation of patients with age and pathology related.The MVD of IL-17 positive expression group was 63.76 ± 19.94,while the negative expression group was 45.63 ± 20.62.The MVD of IL-17 positive expression group in NSCLC group was significantly higher than that in negative expression group(P <0.01).Statistical analysis of the correlation between IL-17 positive expression and MVD in NSCLC tissues(r = 0.652).Suggesting that positive expression of IL-17 in NSCLC is positively related to MVD.2 Effects of IL-17 neutralizing antibody alone and its combination with DC101 on the growth of orthotopic transplanted tumor in miceCompared with the control group,anti-IL-17,DC101 alone and anti-IL-17 +DC101 alone had different inhibitory effects on the growth of transplanted tumor in mice(P <0.01).The anti-IL-17 group was lower than the control group(P <0.01),Combined anti-IL-17 + DC101 decreased compared with Anti-IL-17 group(P<0.05),combined with DC101,Anti-IL-17 + DC101 were decreased,but no statistically significant(P> 0.05).The results showed that anti-IL-17 neutralizing antibody was inhibited by lung cancer transplanted mice after treatment(P <0.01),and IL-17 neutralizing antibody can enhance the antitumor effect of DC101.3 Effects of IL-17 neutralizing antibody alone and its combination with DC101 on angiogenesis in orthotopic transplanted miceThe MVD of control group was 70.4 ± 6.18,while the MVD of Anti-IL-17,DC101 and Anti-IL-17 + DC101 groups were 34.6 ± 3.36,27.2 ± 4.76 and 16.6 ±2.70.Compared with control group,the MVD of anti-IL-17 or DC101 alone and anti-IL-17 + DC101 group was significantly decreased(P <0.01).Compared with DC101 group,The MVD of 17 + DC101 group decreased,which was statistically significant(P <0.05).The results showed that IL-17 neutralizing antibody could inhibit the angiogenesis of lung cancer and IL-17 neutralizing antibody could enhance the anti-angiogenic effect of DC101.4 Effects of IL-17 neutralizing antibody on IL-17 and VEGF in peripheral blood of miceThe expression of IL-17 in the control group was(663.39 ± 40.92)pg / ml and the expression of VEGF was 119.81 ± 3.37 pg / ml.Compared with control group,IL-17 expression in anti-IL-17 group decreased(525.64 ± 57.76),while VEGF expression(70.21 ± 4.90)decreased significantly(P <0.05).Compared with control group,the expression of IL-17(768.32 ± 53.07)in DC101 alone was increased(P>0.05).Compared with DC101 group,the expression of IL-17 in anti-IL-17 + DC101 group was decreased(627.11 ± 60.44),and the expression of VEGF(34.52 ± 3.31)was significantly decreased(P <0.05).The results show that IL-17 neutralizing antibody may reduce the expression of VEGF to inhibit the formation of blood vessels in lung cancer and improve the therapeutic effect of DC01..5 IL-17 neutralizing antibody on immune cells in mouse spleenFlow cytometry was used to detect the percentage of TH17 cells in mice.Compared with control group(15.32 ± 1.89)%,the percentage of Th17 cells(4.41 ±3.10)in the spleen of mice treated with Anti-IL-17 was significantly decreased(P<0.01).while the percentage of Th17 cells(21.91 ± 2.09)increased in the spleen of DC101 group(P <0.05).Compared with DC101,the percentage of Th17 cells(6.10 ±2.06)in the spleen of Anti-IL-17 + DC101 decreased(P <0.01).Compared with control(10.08 ± 0.85),Treg cells in the spleen of the anti-IL-17 group(15.69 ± 1.82)or DC101 group(13.6 ± 0.85)were increased(P <0.05).Compared with the DC101group(13.6 ± 0.85),the percentage of Treg in the spleen of the anti-IL-17 + DC101group(24.1 ± 1.20)increased(P <0.01).The above experiments suggest that IL-17 may promote tumor angiogenesis and may be related to the percentage of immune cells Th17 cells and Treg cells.We can conclude that IL-17 is highly expressed in non-small cell lung cancer and positively correlated with MVD.IL-17 neutralizing antibody can inhibit tumor growth and IL-17 neutralizing antibodies can enhance the anti-vasculine effect of DC101;IL-17 is highly expressed in peripheral blood of tumor-bearing mice and IL-17 may increase MVD by promoting VEGF expression;IL-17 may promote angiogenesis may be related to the proportion of Th17 cells and Treg cells. |
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