The Effect Of CD147 Inhibitor And Activator On GBC-SD Cells

1.Background and ObjectiveGallbladder cancer is the most common biliary tract cancer,Gallbladder cancer early symptoms hidden,rapid disease progression,high degree of malignancy,early diagnosis is more difficult,When patients with abdominal pain,jaundice and other symptoms,often in the late stages of cancer,Low surgical resection rate,insensitivity to radiotherapy and chemotherapy,and poor prognosis.At present,the treatment of gallbladder cancer is still based on surgical treatment,and the postoperative adjuvant therapy plays an active role in prolonging the survival time of the patients with gallbladder cancer.However,the total 5 year survival rate is still not optimistic because of the high degree of malignancy of gallbladder cancer.The key to the treatment of gallbladder cancer lies in early detection,early diagnosis and early treatment.After early diagnosis of gallbladder cancer,the key to improve the survival rate of gallbladder cancer patients is to choose individualized treatment according to the different stages of gallbladder cancer.CD147 is a single stranded transmembrane glycoprotein located on the surface of tumor cell.Its relative molecular mass is about 58 * 103.In the process of metastasis and invasion,CD147 is involved in the basement membrane degradation,revascularization and tumor cell infiltration.The N end of the CD147 molecule is highly glycosylated.The glycosylated CD147 can stimulate the fibroblasts to produce a large number of matrix metalloproteinases(MMPs)in the microenvironment of the tumor.MMPs can degrade extracellular matrix and basement membrane,enhance penetration of tumor cells in matrix,and promote tumor invasion and metastasis.MMP-9 is one of matrix metalloproteinases.Only high glucose based CD147 has the function of inducing MMPs production,and the de glycosylated CD147 has a strong inhibitory effect on MMPs.It has been proved that the expression of CD147 and MMP-9 in the carcinoma of gallbladder is increased,so it is of great significance to study CD147 for the treatment of gallbladder cancer.Angiotensin II can promote the expression of CD147 in various tumor cells,increase glycosylation,and then activate MMPs.Tunicamycin is an antibiotic that blocks the synthesis of N-sugar chain.It can inhibit the processing of sugar chain and form glycoprotein free glycoprotein by inhibiting the activity of transferase.Therefore,tunicamycin can effectively inhibit the biological activity of the CD147 protein by acting on the N end structure of the CD147 protein and making the CD147 protein glycosylated.In this study,we observed the effects of CD147 inhibitor tunicamycin and activator angiotensin II(Ang II)on the proliferation,invasion,CD147 and MMP-9 expression of human gallbladder carcinoma GBC-SD cells,and explored the possible mechanism of its action on GBC-SD cells.2.MethodsTo act on GBC-SD with different concentrations of tunicamycin(5?10?20?l/ml)?Ang?(5?10?20?l/ml)and combination therapy(tunicamycin10?l/ml +Ang?20?l/ml),the rate of proliferation was detected by CCK-8,expression of CD147 and MMP-9 were detected by western blot,the ability of invasiveness detected by Transwell.3.ResultsCompared with the control group,the proliferation rate of tunicamycin group(88.17 ± 8.36?85.35 ± 6.42?82.01 ± 5.41)was lower than that of the control group(100 ± 0.00)(p<0.01),and the expression of CD147(0.75±0.04?0.71±0.04)and MMP-9(0.84±0.04?0.67±0.10)was decreased(p<0.01),and the ability of invasiveness(43.00±10.98?32.46±7.71)was decreased(p<0.01).Compared with the control group,the proliferation rate of Ang?group(105.47 ± 7.06?108.25 ± 6.57?111.51 ± 4.49)was higher than that of the control group(p<0.01),and the expression of CD147(1.02±0.08?1.08±0.05)and MMP-9(1.28±0.06?1.57±0.07)was increased(p<0.01),and the ability of invasiveness(98.00±12.56)was increased(p<0.01).Combination therapy: Compared with group Ang II,cell proliferation rate and invasiveness decreased,CD147 expression and MMP-9 expression decreased compared with group Ang II.4.ConclusionsTunicamycin can inhibit the proliferation of gallbladder cancer cells,reduce the expression of CD 147 and MMP-9,and Ang?can accelerate the proliferation of gallbladder cancer cells,increase the expression of CD 147 and MMP-9,tunicamycin can inhibit the promotion of Ang II.