ObjectiveTo study the expression of matrilysin in gastric cancer and to evaluate the correlation between its expression and invasion, metastasis, and prognosis. MethodsA total of 52 patients with gastric cancer were selected and followed up. The expressions of matrilysin in gastric primary focus, normal gastric mucosa, and metastatic lymph nodes were examined by reverse transcriptionpolymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry, respectively. The correlations between matrilysin expression and tumor invasion, metastasis, and prognosis were assessed. ResultsThe expressions of matrilysin in gastric primary focus and metastatic lymph nodes significantly increased, while decreased or loss in normal gastric mucosa (Plt;0.001). The higher concordance was seen between the levels of mRNA and protein (Plt;0.001). Among patients with infiltrating type, penetrated serosa, area of serosa involved more than 20 cm2, and metastatic lymph nodes more than 7, the expression of matrilysin was significantly higher (Plt;0.01). The survival rate of patients with matrilysin higher expression (34.1%) was significantly lower than that with matrilysin lower expression (55.6%), χ2=9.778， P=0.002. Conclusions Up-regulated expression of matrilysin plays an important role in tumor invasion, metastasis, and poor prognosis, and it is a good molecular marker to reflect the biological behaviors of gastric cancer.
Objectives To explore the effects of curcumin and cisplatin on A549 lung cancer cell invasion and metastasis, and explore the influence of the two drugs on matrix metalloproteinase 9 (MMP-9) and E-cadherin protein. Methods MTT assay was performed to detect the effects of curcumin, cisplatin alone and the combination on A549 lung cancer cell proliferation. Transwell assay was performed to detect the effects of curcumin, cisplatin alone and the combination on the invasion and metastasis of lung cancer cells. Western blot was used to detect the protein expression of MMP-9 and E-cadherin. Results The proliferation inhibition of A549 lung cancer cell rate in 5, 10, 20, 40 μmol/L of curcumin was 6.50%±1.06%, 11.70%±0.88%, 22.97%±0.82%, 27.93%±0.94%, respectively. Compared with control group, the proliferation inhibition rates in four different curcumin groups were significantly increased (all P<0.01). The differences in the proliferation inhibition rates among four different curcumin groups were statistically significant (allP<0.05). The proliferation inhibition rates of A549 lung cancer cell in 1, 2, 4 mg/L of cisplatin were 7.12%±0.86%, 20.07%±1.14%, 26.88%±0.51%, respectively. Compared with control group, the proliferation inhibition rates in three different cisplatin groups were significantly increased (allP<0.01). The differences in the proliferation inhibition rates among three different cisplatin groups were statistically significant (allP<0.01). The proliferation inhibition rates of A549 lung cancer cell in curcumin (20 μmol/L) combined with cisplatin (1, 2, 4 mg/L respectively) were 28.37%±0.57%, 39.72%±0.64%, 46.27%±0.86%, respectively. Compared with control group and curcumin or cisplatin used alone, the proliferation inhibition rates of three combined groups were significantly increased (allP<0.01). The invasion inhibition rates of A549 lung cancer cell in curcumin group (20 μmol/L), cisplatin group (2 mg/L) and combined group (curcumin 20 μmol/L plus cisplatin 2 mg/L) were 38.62%±0.23%, 36.52%±0.33%, 63.78%±0.59%, respectively. Compared with control group and curcumin or cisplatin used alone, the invasion inhibition rates of combined group were significantly increased (allP<0.01). The protein grey values for curcumin group (20 μmol/L), cisplatin group (2 mg/L) and combined group (curcumin 20 μmol/L plus cisplatin 2 mg/L) were 0.768±0.047, 0.654±0.104, 0.684±0.008, 0.444±0.104 (MMP-9) and 0.603±0.170, 0.792±0.050, 0.784±0.045, 0.879±0.110 (E-cadherin), respectively. Compared with control group and curcumin or cisplatin used alone, the protein grey values of combined group were significantly different (allP<0.01 orP<0.05). Conclusions Curcumin and cisplatin combination can inhibit the invasion and metastasis of lung cancer A549 cells. Its mechanism may be related to downregulating MMP-9 and upregulating E-cadherin.
Objective To examine the effects of newly designed LY52 on the expression of matrix metalloproteinases and invasive ability of hepatocellular carcinoma HepG2 cells. Methods The effects of LY52 on the proliferations of HepG2 cells were detected by MTT assay. Gelatin zymography and Western blot were used to detect the effects of LY52 on matrix metalloproteinase-2 expression in the cell line. Transwell chamber assay was used to detect the effects of LY52 on the invasion of the cells. Results No obvious inhibitory or cytotoxicity effects of LY52 was found in lower concentrations (lt;200 μg/ml) of LY52. Gelatin zymography and Western blot showed that matrix metalloproteinase-2 expression were inhibited by LY52 in a dose-dependent manner in HepG2 cells. Furthermore, transwell chamber assay showed that LY52 could significantly inhibit the invasion of the cell line in a dose-dependent manner.Conclusion The results suggest that LY52 may inhibit the invasion of hepatocellular carcinoma cells by suppressing the matrix metalloproteinase-2 activity.
【Abstract】Objective To investigate the correlation of adhesive molecule expressions with potential of invasion and metastasis in papillary thyroid carcinoma (PTC). Methods S-P immunohistochemical method was used to detect CD44v6 and E-cadherin expression in 58 cases of PTC. Results The positive rates of CD44v6 and E-cadherin in PTC were 72.40%and 41.4% respectively. There was a positive correlation between CD44v6 expression and tumor invasive and metastatic potential in PTC (P＜0.05), and a reverse correlation between E-cadherin expression and the potential (P＜0.01).Moreover,there was a reverse correlation between the CD44v6 and E-cadherin expression in PTC(P＜0.05). Conclusion These data show a correlation between the adhesive molecule expression and the potential of invasion and metastasis in PTC. CD44v6 and E-cadherin may be prognostic indicators in PTC.
Objective To observe the effect of epidermal growth factor (EGF) on the proliferation, adhesion, invasiveness and the activation of nuclear factor-κB (NF-κB), matrix metalloproteinases (MMPs) expression and explore related mechanisms in pancreatic cancer cells. Methods Cell invasion assay, proliferation assay and adhesion assay were used to examine the proliferation, adhesion and invasiveness of pancreatic cancer cells, respectively. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA), and MMPs protein and mRNA expressions were investigated by gelatin zymography, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Results EGF increased the invasiveness of pancreatic cancer cell in a dose-dependent manner (P＜0.05), but did not affect cell proliferation or adhesion. The expressions of MMP-9 mRNA and protein significantly increased after induction by EGF and were highest when EGF concentration was 50 ng/ml, while there was no effect on the expressions of MMP-2 mRNA and protein. Furthermore, NF-κB activity increased with increased concentration of EGF in a concentration-dependent manner (P＜0.05). In addition, NF-κB activity and the expressions of MMP-9 mRNA and protein by pretreatment with both pyrrolidine dithiocarbamate (PDTC) and EGF decreased when compared that by pretreatment with EGF alone. The invasiveness of pancreatic cancer cell by pretreatment with both PDTC and EGF decreased when compared that by pretreatment with EGF alone and nothing (P＜0.05).Conclusion The findings indicate that the NF-κB-mediated MMP-9 induction is essential for EGF-induced invasiveness in pancreatic cancer cells, which can be inhibited by PDTC.
【Abstract】ObjectiveTo study the effect of down-regulation of E-cadherin on the invasion ability of tumor cells. MethodsHuman pancreatic carcinoma cell line JHP-1 was treated with E-cadherin antisense oligodeoxynucleotied (ASODN). The immunocytochemistry, Western blot were used to detect the expression and the contents of E-cadherin in the tumor cells, and the invasive ability of tumor cells were evaluated by invasive-MTT assay. Results Treated with E-cadherin ASODN, the expression of E-cadherin on JHP-1 cells were reduced, and the protein contents were decreased as well compared with control groups and ODN group. The invasive ability of JHP-1 cells to the basement membrane was increased (P＜0.001) compared with ODN group and control group. ConclusionE-cadherin was related to the invasive ability of tumor cells.
Objective To summarize the role of matrix metalloproteinases (MMPs) in occurrence and development of gastric cancer. Methods Domestic and international publications online involving MMPs of gastric cancer in recent years were collected and reviewed. Results The occurrence and development of gastric cancer was a multi-step and multi-factorial complicated progress, whose etiology and pathogenesis were still unclarified. MMPs were a class of proteolytic enzymes, which played an important role in the proliferation, metastasis, angiogenesis of gastric cancer and apoptosis of tumor cells and their surrounding normal cells by regulating the microenvironment of the growth of tumor. Conclusion MMPs promote the evolution of gastric cancer in variable ways, the mechanisms of which should be comprehended to provide a theoretical basis for the future treatment of gastric cancer.
Objective To study the expressions of Wnt5a, MMP2, and MMP14 in the primary lesions of gastric cancer and the influences on clinicopathologic features. Methods The expressions of Wnt5a, MMP2, and MMP14 in the specimens of 106 patients with gastric cancer and 39 patients from the adjacent normal gastric tissues were detected by immunohistochemical staining, χ2 test and non-parametric test were used to analyze the relationships among them and between them and their influences on the clinicopathologic features. Results Extensive expressions of Wnt5a, MMP2, and MMP14 were demonstrated in the gastric cancer, which were significantly higher than those in the normal gastric tissues respectively (Plt;0.05). Positive expression of Wnt5a was associated with larger tumor diameter, deeper depth of invasion, higher degree of regional lymph node metastasis, later TNM stage, and higher rate of lymph node metastasis (Plt;0.05). In addition, Wnt5a expression was also associated with lymphatic infiltration and vascular infiltration (Plt;0.05). The expressions of MMP2 and MMP14 were associated with lymphatic infiltration, but not with vascular infiltration. Higher expressions of MMP2 and MMP14 were correlated with deeper tumor invasion, higher degree of regional lymph node metastasis, later TNM stage, and higher rate of lymph node metastasis (Plt;0.05). In addition, higher expression of MMP2 possesed greater tumor diameter (Plt;0.05). Spearman rank correlation analysis revealed the positive relation between Wnt5a and MMP2 （rs=0.240, P=0.014）, Wnt5a and MMP14 （rs=0.251, P=0.010）, as well as MMP2 and MMP14 （rs=0.444, P=0.000）. Conclusion Higher expressions of Wnt5a, MMP2, and MMP14 seem to promote invasion and metastasis of gastric cancer, and there are positive relations among their expressions.
Objective To investigate the expression of c-met in tall cell variant of papillary thyroid carcinoma, and to compare it with other types of thyroid carcinoma and benign thyroid tissue. Methods The expressions of c-met in 60 cases of thyroid specimens were tested by immunohistochemical staining. Results The levels of expressed c-met in tall cell variant specimens were significantly higher than those in other types of papillary thyroid carcinoma and benign thyroid tissue. c-met expressions were significantly different in the following pairs of types: tall cell variant vs common papillary carcinoma of thyroid (P=0.000 1), tall cell variant vs follicular variant papillary thyroid carcinoma (P=0.000 1), and tall cell variant vs benign thyroid tissue (P=0.000 1). In addition, for all types of papillary carcinomas evaluated, c-met expression was significantly higher in specimens with extracapsular spread (P=0.010 0) and skeletal muscle invasion (P=0.020 0). Conclusion The high expression of c-met is a significant marker for tall cell variant papillary carcinoma of thyroid and its invasive behavior. This finding may explain the unusually aggressive behavior of this tumor and suggest a role for c-met in the early identification of patients with tall cell variant thyroid carcinoma.
Objective To investigate the expression of Fascin-1 protein in colorectal adenocarcinoma, and the relationship with its clinicopathologic features. Methods The expressions of Fascin-1 protein in colorectal adenocarcinoma tissues of 60 cases, colorectal adenoma tissues of 30 cases and normal mucosa tissues (4 cm distance to neoplasm) of 30 cases were detected by Microwave-EliVisionTM immunohistochemistry method, and the relationship between the expression of Fascin-1 protein in colorectal adenocarcinoma tissues and its clinicopathologic characteristics was analyzed. Results The expression of Fascin-1 protein was located in cytoplasm. The positive expression rates of Facsin-1 protein were 3.3% (1/30), 30.0% (9/30) and 53.3% (32/60) in normal mucosa tissues, colorectal adenoma tissues and colorectal adenocarcinoma tissues, respectively. The expression of Fascin-1 was gradually increased in these three tissues, and there was statistical difference among the three tissues (Plt;0.05). The expessions of Fascin-1 protein in patients with serous membrane invasion, lymph node metastasis and TNM Ⅲ+Ⅳ were higher than those of non-serous membrane invasion, non-lymph node metastasis and TNM Ⅰ+Ⅱ (Plt;0.05), but there was no significant difference among different differentiation degrees (Pgt;0.05). Conclusion The high expression of Fascin-1 protein is correlated to high invasion ability and lymph node metastasis, which can play as a sensitive index in predicting the invasion and metastasis of colorectal adenocarcinoma.