| [Research Background]Lung cancer is one of the malignant tumors with the highest morbidity and mortality in China and even in the world.With the aggravation of air pollution,the morbidity and mortality of lung cancer are increasing year by year.Lung cancer is divided into small cell lung cancer and non-small cell lung cancer,and NSCLC accounts for 80-85%of the incidence of all lung cancers.Most lung cancer patients are already in advanced stage when they are found,and the overall five-year survival period leading to lung cancer is only 16%.Erchen decoction is a classical prescription for resolving phlegm in traditional Chinese medicine,and phlegm and blood stasis are the basic syndromes of advanced lung cancer.Studies have shown that the progress of lung cancer is closely related to the formation of tumor angiogenesis,and inhibiting the formation of tumor blood vessels is also a commonly used method for targeted treatment of lung cancer at present.The activation of JNK signaling pathway can promote the formation of tumor angiogenesis,thus promoting the occurrence of tumor metastasis.Previous studies by my supervisor showed that erchen decoction containing drug serum could inhibit the proliferation of A549 cell line and icam-1 expression of cell membrane through JNK and P38 pathway.This suggests that erchen decoction may play an anti-tumor role by inhibiting the expression of Icam-1 in tumor cells and inhibiting the JNK pathway,and it also suggests that phlegm-resolving method has its exact role in the treatment of NSCLC.Therefore,this experiment will acknowledge A549 lung cancer cells in nude mice model,based on the experimental animals oral Erchen Decoction and its combined with cisplatin chemotherapy in vivo animal experiments,detection of nude mice tumor tissue of P-JNK,P-P38 lightning,VEGF,VEGF1,VEGF2,VCAM protein content to observe whether TCM phlegm method can have inhibition effects on tumor angiogenesis,thus the progress of the inhibition of lung cancer.[Research purposes]To determine whether erchen decoction can interfere with tumor angiogenesis of NSCLC by inhibiting the JNK signaling pathway,and to further clarify the mechanism of erchen decoction in the treatment of NSCLC,as well as the microscopic effect of TCM phlegm resolving method in the treatment of NSCLC[Research methods]In this experiment,the nude mice bearing A549 lung cancer cells were established in nude mice.Sixty nude mice were divided into 6 groups by random numerical table method:normal saline,Erchen decoction and Erchen decoction,and Erchen decoction was used to break blood and remove blood stasis,and the mice were divided into 6 groups by random numerical table method.Yiqi Yangyin Huatan Sanjie prescription and cisplatin group as positive control group for intervention,14 days later,the treatment group and the control group of each difference,compare the size of tumor in each group,calculate the tumor inhibition rate;After intervention of Erchen decoction on nude mice,Western blot method was used to detect the levels of PJK,Pp38,VEGF and VEG in tumor of nude mice.Expression of FR-1,VEGFR-2,VCAM-1 protein.The experimental data were analyzed by SPSS 21.0(P<0.05).[Research result]1.erchen decoction high-dose group,erchen decoction combined with traditional Chinese medicine for breaking blood and stasis and cisplatin could inhibit the tumor progression of lung cancer in nude mice,and the tumor inhibition rates were 13.95%(P<0.05),16.94%(P<0.05)and 20.83%(P<0.01),respectively.Compared with the control group,the difference was statistically significant.However,the survival activity of tumor-bearing nude mice in the TCM group was better than that in the cisplatin group.2.the expression level of p-jnk protein in the high-dose erchen decoction group was significantly lower than that in the control group(P<0.05).In the cisplatin group,the expression level of p-jnk protein was significantly decreased,with statistical difference compared with the control group(P<0.05).However,there was no significant difference between the cisplatin group and the erchen decoction group(p>0.05).The expression level of p-jnk protein in nude mice was also decreased after erchen decoction intervention,but the difference was not statistically significant(P>0.05).3.in the large dose group of erchen decoction,the expression level of p-p38 protein was significantly decreased,which was statistically different from that of the control group(P<0.05).The expression level of p-p38 protein in cisplatin group was significantly lower than that in the control group(P<0.05).The expression level of p-p38 protein in the erchen decoction group was significantly lower than that in the control group(P<0.01).However,there was no significant difference among the three groups(p>0.05).4.the VEGF protein expression was significantly decreased in the erchen decoction group compared with the control group(p<0.05),and was significantly decreased in the cisplatin group compared with the control group(p<0.05).Professor Wang Pei experience side group,its amount of VEGF1 protein expression decreased significantly,compared with the control group with statistical difference(p<0.05),cisplatin group,its amount of VEGF1 protein expression decreased significantly,compared with the control group with statistical difference(p<0.05),while second Chen Shang group of Chinese medical VEGFR-1 protein expression in tumor tissue of nude mice content compared with the control group had no statistical difference(p>0.05);Two Chen Shang high-dose group of VEGFR-2 protein expression level decreased significantly,compared with the control group with statistical difference(p<0.05),and the second Chen Shang add broken blood by blood stasis of TCM in the tumor tissue of nude mice the expression of VEGFR-2 protein content decreased significantly,compared with the control group with statistical difference(p<0.05),professor Wang Pei experience group of nude mice tumor tissue in the expression of VEGFR-2 protein content decreased significantly,compared with the control group has significant statistical difference(p<0.01),cisplatin group,the expression of VEGFR-2 protein content decreased significantly,Compared with the control group,there was significant statistical difference(p<0.05),and there was no statistical difference between the four groups(p>0.05).5.the expression of VCAM protein in erchen decoction group and erchen decoction group plus traditional Chinese medicine of breaking blood and stasis was inhibited,but there was no statistical difference(p>0.05).[Research conclusion]1.erchen decoction and erchen decoction combined with traditional Chinese medicine of breaking blood and stasis and cisplatin could inhibit the development of lung cancer masses in nude mice.However,the survival activity of tumor-bearing nude mice in the TCM group was better than that in the cisplatin group.2.the expression of p-jnk protein in nude mice of erchen decoction and cisplatin group was significantly decreased,so it was believed that it could inhibit the progression of lung cancer by blocking the JNK signaling pathway.3.the expression levels of p-p38 protein in nude mice of erchen decoction and erchen decoction were significantly decreased with the addition of the traditional Chinese medicine of "breaking blood and chasing stasis" and cisplatin group,so it was believed that erchen decoction could also inhibit the progress of NSCLC by blocking the p-38 pathway.The blocking effect of erchen decoction on the p-38 pathway was stronger after the addition of the traditional Chinese medicine of "breaking blood and chasing stasis" in erchen decoction.4.The expression levels of VEGF protein in erchen tang and cisplatin group were significantly decreased.The VEGF1 protein expression level of the nude mice in professor wang pei’s empirical formula group was significantly decreased,while there was no significant change in erchen tang group.The expression level of vegfr-2 protein in erchen decoction,erchen decoction,and professor wang pei’s empirical prescription group was significantly decreased,and the expression level of VEGF2 protein in nude mice in professor wang pei’s empirical prescription group was significantly decreased.Therefore,it can be concluded that erchen decoction can inhibit the formation of tumor blood vessels.which mainly plays a role by inhibiting vegfr-2 protein.Conclusion:erchen decoction can inhibit the progression of lung cancer by inhibiting tumor angiogenesis,and the mechanism is related to erchen decoction’s inhibition of JNK signaling pathway and p-38 pathway. |
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