Yiqi Yangyin, Huatan Quyu Recipe Inhibits Lung Cancer Angiogenesis By Regulating IL-17 And Its Partial Mechanism

[Objectives]To clarify whether Huatan Quyu and Yiqi Yangyin Fang(HQYYF)can regulate VEGFR-2 expression through IL-17,and further clarify whether its effect is carried out through the STAT3 signaling pathway,and to deepen the molecular mechanism research of HQYYF.Finally,we hope to provide a new basis for the rational and effective application of HQYYF in clinical practice.[Methods]In this study,a Lewis lung cancer mouse model was established,and 31 tumor-bearing mice were randomly divided into a model group,a Chinese medicine group,a Chinese medicine combined with cisplatin group,and a cisplatin group.There were 4 groups in total,7 in the model group,and 8 in the remaining three groups.The model group was treated with 0.4ml/20g normal saline,the Chinese medicine group was given 0.4ml/20g HQYYF,and the Chinese medicine combined with cisplatin group was given 0.3mg/ml cisplatin solution 200ul/20g by intraperitoneal injection,dosing on days 1,4,and 7,and 0.4m1/20g Chinese medicine decoction was given to the stomach,and the cisplatin group was given 0.3mg/ml cisplatin solution 200?L/20 g by intraperitoneal injection,dosing on days 1,4,and 7.and 0.4 mL/20 g normal saline by gastric lavage once a day for 15 consecutive days.During the observation,the survival status of Lewis mice was observed.After gastric gavage.the mice were sacrificed,and the body weight,tumor weight and spleen weight of the mice were weighed to calculate the tumor suppression rate and spleen index.HE staining was used to observe the pathological morphologic changes of tumor tissue in each group.Enzyme linked immunosorbent assay(ELISA)was used to detect the changes of IL-17 expression in serum of Lewis lung cancer mice in each group;Immunohistochemistry(IHC)was used to detect the changes of VEGFR-2 and STAT3 expression in tumor tissue of each group.[Results]1.On the 5th day of inoculation,a soybean-sized mass was touched subcutaneously in the right armpit of the mouse,and the tumor growth significantly accelerated on the 7th day.With the growth of tumors,hair loss,lack of luster,slow response,aggregation,and decreased food intake were gradually observed in each group.Compared with the model group,the cisplatin group,and the combined group,the mice in the Chinese medicine group were more active and more viable.They were generally better than the other three groups,and their quality of life was relatively better.2.The tumor inhibition rates of the Chinese medicine group,the combined group and the cisplatin group were 28.99%,56.34%,and 57.99%,respectively.Compared with the model group,the tumor weight of Lewis mice in the Chinese medicine group,the combined group and the cisplatin group was significantly reduced,and has statistical differences(P<0.05,P<0.01).Compared with the cisplatin group,the tumor weight of the Chinese medicine group was significantly higher,and has statistical differences(P<0.05).There was no statistical difference in tumor weight between the combined group and the cisplatin group(P>0.05).3.Compared with the model group,the spleen index of the combined group and the cisplatin group descended significantly,and the difference was significant(P<0.01).The spleen index of the Chinese medicine group increased.but the difference was not significant(P>0.05).Compared with the control group,the spleen index of the model group and the Chinese medicine group increased,and the difference was statistically significant(P<0.01).The spleen index of the combined group increased,but the difference was not significant(P>0.05).4.Tumor cells in the model group had higher growth density,larger nuclei and deeper nuclear staining,uneven cytoplasm distribution,less pyknosis,and no obvious cell necrosis and apoptosis.Compared with the model group,the tumor cells were denser in the Chinese medicine group.The degree of cell decreased and the cells were arranged irregularly.In the cisplatin group and the combined group,tumor cells had incomplete structure.reduced volume,irregular arrangement,and necrosis of flaky cells5.Compared with the model group,the serum IL-17 content of Lewis mice in the Chinese medicine group,the combined group and the cisplatin group was significantly reduced,and the difference was statistically significant(P<0.01).There was no significant difference in IL-17 content in mice(P>0.05)6.Compared with the model group,the levels of STAT3 protein in the Chinese medicine group,the combined group,and the cisplatin group decreased,but there was no significant difference between the groups(P>0.05).Statistical differences(P<0.05);compared with the cisplatin group,the differences in the expression of STAT3 and VEGFR-2 in the combined group and the cisplatin group were not statistically significant(P>0.05)[Conclusions]HQYYF can improve the survival status of mice,pay more attention to the overall quality of life of the body,have a certain tumor suppressing effect.have less effect on spleen growth,and have a certain reversal effect on spleen damage caused by cisplatin.Cisplatin has obvious anti-tumor effect,but it has certain side effects on the body.It has inhibitory effect on spleen growth and obvious damage to immune function.The combination of HQYYF and cisplatin has a tendency to improve the immune function of Lewis mice,but has not shown a significant joint effect in inhibiting tumor growth.HQYYF and Cisplatin can all reduce the serum IL-17 content and VEGFR-2 protein expression in Lewis lung cancer mice,and have a tendency to down-regulate STAT3.It is inferred from this that HQYYF may be able to inhibit the expression of VEGFR-2 by down-regulating the content of IL-17 and inhibit the angiogenesis of lung cancer tumors.However,HQYYF combined with cisplatin did not show better effects in reducing serum IL-17 content and reducing VEGFR-2 in lung cancer mice than cisplatin.