| Background:Cervical cancer is one of the most common malignant tumors of female genital tract,China's new cases each year accounted for the world's total number of new cases of cervical cancer 1/3,about 13.15 million,died of cervical cancer patients each year about 5 million people[1]Although the combined treatment of surgery,radiotherapy and chemotherapy has significantly improved the prognosis of cervical cancer patients,but the occurrence of lymphatic metastasis of cervical cancer treatment is still unsatisfactory.Lymphatic metastasis is one of the most common and important metastatic pathways in cervical cancer,and it is also an important factor affecting the prognosis of patients.Maspin gene is a member of serine protease inhibitor.With the deepening of maspin research,it has been found that it has obvious inhibitory effect on the growth,invasion and metastasis of mammary gland and prostate.In recent years,Generation factor study found that vascular density and micro-lymphatic density is one of the prognostic markers of multiple solid tumors[2].Phosphotyrosinositol-3 kinase/serine-threonine kinase(PI3K/Akt)signal transduction pathway is an important step in regulating cell proliferation and maintaining the malignant biological characteristics of cells.One of the guideways[3].Studies have shown that AKT pathway in tumor lymphangiogenesis and lymph node metastasis plays an important role[4].Maspin is a new type of gene found in Zou et al.In 1994 using subtractive hybridization techniques in breast cancer tissues and normal breast tissues,and maspin belongs to a new member.[5]Narayan et al[6]studies confirmed that maspin gene by inhibiting the formation of fibroblasts and VEGF and inhibit vascular production.The high expression of Maspin gene is negatively correlated with the resistance of tumor cells,and the apoptosis rate of malignant tumor cells can be increased.It is also proved that the expression of maspin gene is an important index to guide the prognosis[7][8].Namie et al.[7]injected the plasmid containing the maspin gene into the nude mice bearing the NCIH157 lung cancer cell line.The tumor volume containing the maspin gene plasmid was much smaller than that of the control group(P<0.05),indicating that the maspin gene was Gene therapy has a broad prospect.In addition,a large number of clinical trials and animal experiments confirmed that maspin gene expression has inhibited the invasion,tumor cell migration,inhibition of tumor angiogenesis characteristics[9][10][11][12].In recent years,the study of tumor micro-lymphatic vessels has become a hotspot.A large number of experiments have shown that[13][14][15][16]maspin gene is closely related to the regulation of tumor micro-lymphangiogenesis.PI3K/AKT pathway plays an important role in tumor cell proliferation,migration and invasion and anti-apoptotic effects[17].In addition,studies have shown that E7 protein secreted by human papillomavirus 16(HPV16)can activate AKT pathway to regulate the proliferation and metastasis of tumor cells[18],which is closely related to the development and progression of cervical cancer.The treatment of human papillomavirus is also the prevention of cervical An important means of cancer.Chen et al.[19]used immunohistochemistry to detect the expression of mTOR,AKT,VEGF-C,VEGF-D and lymphatic density in 55 cases of gastric adenocarcinoma.The results showed that lymphatic density was correlated with mTOR,AKT,VEGF-C and VEGF-D were positively correlated.Yang et al found that leptin could promote the secretion of VEGF-C through PI3K/AKT pathway in chondrosarcoma and promote the production of tumor micro-lymphatic vessels.Indicating that abnormal activation of AKT pathway may be an important pathway for the development of many cancers and lymph node metastasis.Therefore,the question we raised is whether the role of the maspin gene in inhibiting tumorigenesis,progression,and inhibition of tumor micro-lymphangiogenesis is related to the PI3K/AKT pathway,which we discuss how to inhibit tumor lymphatic metastasis and target therapy for tumor therapy Has important significance.Objective:This study was to investigate the effect of Maspin gene expression on AKT and P-AKT expression in cervical squamous cell carcinoma and whether the Maspin gene could affect the process of lymphangiogenesis and lymph node metastasis by influencing the expression of AKT pathway.Methods:Collected from February 1,2009 to February 1,2016,Binzhou Medical College Affiliated Hospital of 107 cases of cervical paraffin tissue specimens(20 cases of chronic cervicitis,LSIL 20cases,HSIL 20 cases,47 cases of cervical cancer,cervical(1)group,lymph node metastasis was cervical cancer(2)group.Immunohistochemical SP method was used to detect the expression of maspin and AKT in the patients with lymph node metastasis,P-AKT expression and Lymphatic microvessel density(LMVD).Results:The positive rate of Maspin protein in HSIL group was significantly higher than that in cervical cancer group(P<0.05).The positive rate of Maspin protein in HSIL group was significantly higher than that in cervical cancer group(P<0.05))Group P = 0.005,the difference was statistically significant(P<0.05).The positive rate of maspin protein in cervical cancer(1)group was 39.19%,the positive rate of cervical cancer(2)group was 13.3%,the positive rate of maspin protein decreased,but there was no significant difference between the two groups(P = 0.264).The positive expression rate of AKT and P-AKT in different cervical tissues increased gradually.The expression of AKT and P-AKT in cervical cancer was mainly located in the cytoplasm,and the small part was located in the nucleus of cervical cancer cells.The expression of maspin protein in cervical squamous cell carcinoma was negatively correlated with the expression of AKT and P-AKT.The expression rates of AKT and P-AKT in cervical cancer(1)and cervical cancer(2)were significantly higher than those in other groups(P<0.05).AKT and P-AKT were significantly higher in HSIL group and cervical(P<0.05).There was no significant difference in the expression of AKT between cervical cancer(1)and cervical cancer(2),but there was no significant difference between the two groups(P<0.05)(P = 0.042).Meanwhile,we found that the expression of AKT in cervical cancer was not correlated with LMVD,the expression of P-AKT and the expression of LMVD in cervical cancer(1)and cervical cancer(2)group were statistically significant(P = 0.042)Positive correlation.Conclusion:With the progress of cervical lesions maspin protein expression decreased gradually,AKT,P-AKT expression gradually increased,cervix HSIL expression of maspin was significantly higher than cervical cancer,maspin protein may indicate that cervical HSIL to cervical cancer plays an important process The expression of maspin protein in cervical cancer was negatively correlated with the expression of AKT and P-AKT.The expression of P-AKT was positively correlated with LMVD and lymph node metastasis.The expression of maspin protein could lead to PI3K/AKT Abnormal activation of the pathway,abnormal activation of the PI3K/AKT pathway promotes the production of tumor micro-lymph,leading to lymph node metastasis of tumor cells. |
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