| A world health organization data show that each year about 1.6 million people died of lung cancer,and lung cancer has become the world's highest morbidity and mortality of malignant tumor.Also our country has the largest number of lung disease,and each year about 730000 people have been diagnosed with lung cancer.With the rapid development of industrialization which has led to serious haze phenomena and smoking rates increases,the incidence of lung cancer are rapidly increasing in our country,and it has become the first place of death in our country population malignant tumors.With the continuous improvement of the level of medical technology and the gradual improvement of their treatment methods,the means of current treatment of lung cancer include chemical therapy,radiotherapy,surgery,minimally invasive treatment,immunization and Chinese medicine treatment,but no matter what kind of treatment disease,poor prognosis and the overall effect of treatment is not optimistic,so the search for new methods is imminent.The occurrence of malignant tumor,growth and metastasis depend on angiogenesis,so inhibiting angiogenesis can suppress tumor development.The key to the regulation of tumor angiogenesis is the angiogenesis promoting factor and the inhibitory factor,so controlling the dynamic balance of the two is a vital step in the treatment of tumors.Chemokine CXCL16 is a new chemokine found in recent years.It belongs to the family of CXC chemokines and has many biological activities,which mediate intercellular adhesion and angiogenesis.Tumor necrosis factor alpha(TNF-?)is the most recognized anti-tumor effect factor,both with the receptor binding induced tumor cell apoptosis,but also the role of tumor vascular endothelial cells,leading to vascular dysfunction,Thereby inhibiting tumor growth.Tetramethylpyrazine(TMP)is an effective component of Huoxue Huayu Chuanxiong Chuanxiong,which has anti-tumor angiogenesis,but the mechanism needs further study.Cisplatin(cis-diamminedichloroplatin,DDP)is the first synthetic platinum anticancer drugs,simple structure,the mechanism is clear,is one of the commonly used chemotherapy drugs.In recent years,many domestic scholars have shown that tumor chemotherapy drugs and angiogenesis in combination with traditional Chinese medicine,can significantly increase the anti-tumor effect of chemotherapy drugs.In this study,the effects of ligustrazine and cisplatin on body weight,tumor volume,tumor weight and expression of CXCL16 and TNF-? were studied by Lewis lung adenocarcinoma.The aim of this study is to elucidate the possible mechanism of antitumor angiogenesis of ligustrazine and cisplatin,and to explore effective antitumor drugs,which will lay an experimental theoretical foundation for the new strategy of anti-tumor drug use in the future.Specific experimental research as follows.The mice were transplanted into mouse lung adenocarcinoma cells.The cells with good logarithmic growth were selected and the diluted cells were injected into the right axillary subcutaneously of 5 to 6 weeks old healthy male C57 BL / 6 mice.(NS,0.9% NaCl),cisplatin group(DDP,2 mg · kg-1)were randomly divided into four groups: normal saline group(NS group,0.9% NaCl group)and cisplatin group(DDP,2 mg · kg-1)(TMP + 100 mg · kg-1),combined group(TMP + DDP,the same dose),each group of 16.On the 14 th day after inoculation,the rats were given intraperitoneal injection for 2 weeks.The mental state of the mice was observed every day.The diameter of the subcutaneous tumor was measured and the tumor volume was calculated every day.The mice were sacrificed 24 hours after the end of the administration.The right axillary subcutaneous tumor was sacrificed and the tumor weight was calculated.The tumor tissue was fixed with the fixative solution.The expression of CXCL16 and TNF-? were detected by immunohistochemical SP method and enzyme-linked immunosorbent assay(ELISA).After the end of the treatment,the mice were treated with saline group as the control,and the effects of the survival status of the mice and the side effects of the chemotherapy drugs on the mice were evaluated by observing the mental status,activity,diet status,tumor size and weight of the mice.The results showed that the mice in the Ligustrazine group had better growth rate and the growth rate of the subcutaneous tumor was faster than that of the normal saline group.The mice in the cisplatin group had the worst living condition,lack of energy,,Hair removal and other phenomena,subcutaneous tumor growth rate is slow.The general condition of the combination group was better than that of the cisplatin group,and the growth rate of the subcutaneous tumor was the slowest.The volume of subcutaneous tumor in each model group was: normal saline group,ligustrazine group,cisplatin group and combined group.The relationship between the subcutaneous tumor weight in the model group was: the saline group> the ligustrazine group> the cisplatin group> the combined group,the tumor inhibition rate was: ligustrazine group(21.69%),cisplatin group(40.74%),combined group(P <0.05).There was no significant difference between the two groups(P> 0.05).The results showed that both ligustrazine and cisplatin had the effect of inhibiting tumor growth.Tetramethylpyrazine was more effective than cisplatin,and tetramethylpyrazine combined with cisplatin had the strongest antitumor effect.The tumor cells were observed by transmission electron microscopy(TEM).The cell membrane defects,endoplasmic reticulum expansion and degranulation,mitochondrial abnormalities,structural disorders,nucleus enlargement,nucleolus fragmentation and chromatin margins were observed.The ultrastructural changes of cisplatin cells were significantly higher than those of ligustrazine group.The cells in the combined group were the most obvious,the cells were rounded,the chromatin condensation,the blockage,the cytoplasm shrinkage,the cytoplasm,the organelles and the nuclear fragments Dead body,by the surrounding cells swallowed.The expression of CXCL16 and TNF-? was detected by immunohistochemistry SP method.CXCL16 expression was positive in the four groups,compared with the saline group(41.27 ± 7.61)× 103,the ligustrazine group(26.31 ± 3.67)× 103,The expression of cisplatin(25.46 ± 3.46)× 103 and the combination therapy group(16.59 ± 4.39)× 103 was significantly decreased,and the expression of the combination group was the lowest(P <0.05).(15.42 ± 3.18)× 103,cisplatin group(16.16 ± 3.69)× 103,and the combination therapy group(12.78 ± 5.14)× 103,and the expression of TNF-? was significantly higher than that of the control group(22.57 ± 4.51)× 103 expression was significantly increased,and the combination of treatment group the highest expression,the difference was statistically significant(P <0.05).The expression of CXCL16 and TNF-? was detected by enzyme-linked immunosorbent assay(ELISA).CXCL16 expression was positive in the four groups.Compared with the saline group(117.74 ± 7.61),the ligustrazine group(102.78 ± 6.12),cisplatin group(101.38 ± 5.49)and combined treatment group(80.94 ± 5.78)were significantly decreased,and the expression of the combination therapy group was the lowest(P <0.05).TNF-? was positively expressed in the four groups,compared with the saline group(54.69 ± 7.45),the expression of the ligustrazine group(60.46 ± 4.17),the cisplatin group(61.39 ± 1.02)and the combined treatment group(68.58 ± 0.12)(P <0.05),and the difference was statistically significant(P <0.05).The expression of CXCL16 and TNF-? was detected by immunohistochemistry and enzyme-linked immunosorbent assay(ELISA).The results showed that both ligustrazine and cisplatin could decrease the expression of CXCL16 in Lewis lung cancer and increase the expression of TNF-The combination of the two drugs can further enhance the inhibition of CXCL16 expression,as well as the promotion of TNF-? expression.In summary,tetramethylpyrazine has anti-tumor growth and enhance the body's immune function,combined with cisplatin can enhance the efficacy of chemotherapy and reduce cisplatin in the course of chemotherapy side effects.Tetramethylpyrazine combined with cisplatin may play an anti-tumor effect by up-regulating the expression of TNF-? and decreasing the expression of CXCL16. |
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