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Objective:To investigate the expression of MACC1 in Klatskin tumor and the relationship between the clinicopathological features and prognosis and the expression of MACC1.Methods:Immunohistochemistry staining was employed to assess the expression of MACC1 protein in Klatskin tumor tissues and matched adjacent non-tumor bile duct tissues.Quantitative real-time PCR was performed to examine MACC1 mRNA expression in Klatskin tumor tissues and the adjacent non-tumor bile duct tissues and normal bile duct tissues.The correlation between MACC1 expression and the clinicopathological features and prognosis was analyzed.Results:The positive rate of MACC1 in Klatskin tumor tissues was significantly higher than that in matched adjacent non-tumor bile duct tissues(P＜0.05).MACC1 mRNA expression in carcinoma tissues was significantly higher than that in the non-tumor bile duct tissues and normal bile duct tissues(P＜0.05).MACC1 expression in Klatskin tumor tissues was related to tumor size,recurrence and lymphatic metastasis(P＜0.05).Survival analysis indicated that the 1-year,3-year,5-year survival rate were with significantly differences between the two groups (P＜0.05).Conclusion:MACC1 expression was significantly higher in Klatskin tumor and it was related to the tumor size,recurrence and lymphatic metastasis.It would affect the prognosis of patients.
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Objective To explore the effect of silencing metastasis-associated in colon cancer 1 ( MACC1 ) gene on proliferation and invasion of cervical cancer Hela cells. Methods siRNA MACC1 and siRNA NC were transfected into cervical cancer Hela cells with liposomes. The expression of MACC1 protein and mRNA was detected by western blot and RT-PCR. Cell viability and invasion ability were measured by MTT and transwell assay, respectively. The expression of cyclin D1, cyclin E matrix metalloproteinase 2 (MMP2), MMP9 and the level of extracellular regulated protein kinases ( ERK) phosphorylation was detected by western blot. Results Compared with siRNA NC, the expression of MACC1 protein and mRNA was down-regulated, cell viability and invasion ability were reduced ( P < 0. 01 ) , cell cycle was arrested at G1 phase (P < 0. 01), the expression of cyclin D1, cyclin E, MMP2, MMP9 and p-ERK1/2 was down-regulated (P< 0. 01). Conclusions siRNA MACC1 can inhibit proliferation and invasion of cervical cancer Hela cells, which migiht be related to down-regulation of p-ERK.
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Objective To explore the effect of silencing metastasis-associated in colon cancer 1 ( MACC1 ) gene on proliferation and invasion of cervical cancer Hela cells. Methods siRNA MACC1 and siRNA NC were transfected into cervical cancer Hela cells with liposomes. The expression of MACC1 protein and mRNA was detected by western blot and RT-PCR. Cell viability and invasion ability were measured by MTT and transwell assay, respectively. The expression of cyclin D1, cyclin E matrix metalloproteinase 2 (MMP2), MMP9 and the level of extracellular regulated protein kinases ( ERK) phosphorylation was detected by western blot. Results Compared with siRNA NC, the expression of MACC1 protein and mRNA was down-regulated, cell viability and invasion ability were reduced ( P < 0. 01 ) , cell cycle was arrested at G1 phase (P < 0. 01), the expression of cyclin D1, cyclin E, MMP2, MMP9 and p-ERK1/2 was down-regulated (P< 0. 01). Conclusions siRNA MACC1 can inhibit proliferation and invasion of cervical cancer Hela cells, which migiht be related to down-regulation of p-ERK.
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Objective To explore the expression of Metastasis-associated in colon cancer-1 (MACC1) in patients with nasopharyngeal carcinoma (NPC), and its relationship with clinical pathologic characteristics and prognosis Methods The expression of MACC1 was detected in 130 cases of NPC and the relationship among the MACC1 expressions, clinical pathologic characteristics and prognosis of NPC was analyzed. Results Positive expression rate of MACC1was 68.5% in the NPC and MACC1 expression was associated with advanced T stages, lymph node metastasis and advanced clinical stages of NPC (P < 0.05). The results of Kaplan-Meier survival analysis showed that the five year overall survival rate in patients with positive expressions of MACC1 (45.9%) was significantly lower than that of those with negative expressions (73.7%) and the difference was statistically significant (P < 0.05), Cox multi-factor analysis results showed that MACC1 expression was an independent prognostic factor for NPC (P = 0.004). Conclusion MACC1 abnormal expression is closely related to the invasion and metastasis of NPC and it is expected to become a new target for gene therapy of NPC.
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Objective To investigate the effect of irinotecan hydrochloride combined with cisplatin on B-cell lymphoma-2 (Bcl-2) and metastasis-associated in colon cancer-1 (MACC1) protein expressions in cervical epithelial tissue of cervical cancer patients.Methods 100 patients with cervical cancer from January 2010 to January 2013 in Department of Obstetrics and Gynecology of Shangrao City People's Hospital were selected as objects.All patients were treated with irinotecan hydrochloride and cisplatin for combination chemotherapy.The clinical effect and the protein expressions of Bcl-2 and MACC1 of cervical epithelial tissue were compared pre-and post-chemotherapy.Results The total efficiency was 75.0%(75/100) after cervical cancer patients were given irinotecan hydrochloride combined with cisplatin chemotherapy program.The expressions and high expression rates of Bcl-2 and MACC1 post-chemotherapy were significantly lower than that pre-chemotherapy(P<0.05) .In clinically effective group, the high expression rates of Bcl-2 and MACC1 post-chemotherapy significantly reduced than pre-treatment (P<0.05), and in clinical invalid group, the difference of the high expression rates of Bcl-2 and MACC1 had no statistically significant.Conclusion After combination chemotherapy with irinotecan hydrochloride and cisplatin on cervical cancer, the expression of Bcl-2 and MACC1 in cervical epithelial tissue significantly reduce, and the clinical efficacy is aignificant.
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Objective To investigate effect of irinotecan combined with cisplatin on level of Bcl-2 and MACC1 protein in serum in patients with cervical cancer.Methods 92 cases of patients with cervical cancer surgery from department of gynaecology and obstetrics,the third People’s hospital of Nanchang were randomly divided into control group and treatment group.Control group was treated with paclitaxel therapy chemotherapy, treatment group were treated with irinotecan combined with cisplatin.Bcl-2 and MACC1 protein in serum were compared before and after the treatment. Results The level of Bcl-2 and MACC1 in both groups were not statistically significant pre-treatment;After treatment, the levels of Bcl-2 and MACC1protein in serum were decreased (P0.05).Death cases of treatment group and control group were 4 cases and 12 cases respectively. the survival rate of 91.30% and 73.91% respectively within one year (χ2 =4.84, P <0.05 ) Conclusion Irinotecan combined with cisplatin in the treatment of cervical cancer in one year survival rate is higher, which may be related to the decrease of serum levels of Bcl-2 and MACC1 protein content.
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Objective This study is to investigate the expressions of MACC1 and c-Met genes in prostate cancer tis?sues and to explore the relationship between these gene expressions with the development, invasion and metastasis of pros?tate cancer. Methods The expressions of MACC1 and c-Met genes were examined in 30 cases of benign prostatic hyperpla?sia and 67 cases of prostate cancer using citron acid-microwave-SP immunohistochemical method and analysed with their clinical pathological features. Results Expressions of MACC1 and c-Met in prostate tissues show statistical difference ac?cording to Gleason score, PSA level, pathological stages and whether bone metastasis occurs after radical surgery ( P<0.05 or P < 0.01), but their expressions in prostate tissue show no significant difference among different sex, age and whether smoking or not. Expression of MACC1 in prostate tissue of stageⅢandⅣcancer is significantly higher than that in benign prostatic hyperplasia (BPH) tissues (P<0.05) while the expression of c-Met only shows statistical difference in prostate tis?sue of stage Ⅳcancer compared with that in BPH (P < 0.05). There is a positive correlation between the expression of MACC1 with expression of c-Met in prostate cancer tissues (P<0.01). Kaplan-Meier curves revealed that the survival rates was lower and survival time of bone-free metastasis were shorter in patients with high MACC1 and c-Met expressions in prostate tissue than those with low expressions of MACC1 and c-Met in prostate tissue. Conclusion Expression of MACC1 and c-Met is closely related to the development, invasion and metastasis of prostate cancer, so MACC 1 and c-Met may be used as promising diagnostic and prognostic markers for prostate tumor, and as new therapeutic targets for prostate cancer.
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Objective:To illustrate the role of miRNA-143 on the invasiveness of cervical cancer cells. Methods:MiRNA-143 mimics or inhibitor sequences were transiently expressed in the cervical cancer cells by liposome transfection. Transwell assay was ap-plied to test the invasive ability of cervical cancer cells after miRNA-143 over-expression or inhibition. Bioinformatics assay was used to predict the targets of miRNA-143. RT-qPCR and luciferase reporter assay were performed to detect the expression of MACC1 mRNA in the cancer cells. RT-qPCR was conducted to test the expression of miRNA-143 and MACC1 mRNA in 20 fresh primary cervi-cal cancer and their matched para-neoplastic tissues. Statistical analyses were performed to evaluate the association between the expres-sion of miRNA-143 and MACC1 mRNA in the 20 cases of cervical cancer. Results:Transwell assays revealed that the miRNA-143 over-expression inhibited the cell invasiveness, while miRNA-143 inhibition promoted the invasive ability of the cervical cancer cells. Bioinformatics analyses revealed that miRNA-143 could target the 3'-UTR of MACC1. Dual luciferase reporter assay confirmed that miRNA-143 can affect 3'-UTR sequence in MACC1 genes. RT-qPCR analyses indicated that the expression of MACC1 mRNA was ob-viously down-regulated after miRNA-143 over-expression, while significantly increased after the miRNA-143 inhibition. The migration in Caski/miRNA-143 inhibitor cells was obviously elevated after being transfected with MACC1 shRNAs. RT-qPCR analyses showed that the expression of miRNA-143 was obviously decreased in the cancer tissues compared with the normal tissues, while MACC1 mRNA was apparently decreased in cancer tissues compared with the normal ones. Statistical analyses revealed that miRNA-143 was negatively correlated with MACC1 mRNA in the 20 cases of cervical cancer. Conclusion:This study reveals that miRNA-143 is down-regulated in the cervical cancer tissues. MiRNA-143 may play an important role in the regulation of cell invasiveness by targeting MACC1 in the cervical cancer cells.
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Objective To study the effects of MACC1 down-regulation on the growth of gastric adenocarcinoma cells. Methods siRNA (MACC1-siRNA1 and MACC1-siRNA2) that can transiently silenced MACC1 was designed, syn?thesized and transfected into MGC-803 cells by lipofectamine 2000. Non-specific siRNA was transfected to be used as nega?tive control. The efficiency of MACC1 depletion was determined by Real-time quantitative PCR. MTT, colony formation and flow cytometry assay were performed to examine cell proliferation. The expressions of MACC1, P21,CDK4, CCND1 and c-myc were determined by Western blot. Results Compared with cells in negative control group, transiently silencing MACC1 decreased the expression of MACC1 in MGC-803 cells shown by Real-time PCR. MACC1 downregulation drastical?ly changed the proliferation, colony formation and cell cycle of gastric adenocarcinoma cells in vitro ( P<0.05). The expres?sions of MACC1 , CDK4, CCND1 and c-myc proteins in cells of MACC1 silence group were much lower while P21 expres?sion level was much higher than those in negative control. Conclusion Down-regulation of MACC1 result in blocking cell cycle, inhibiting proliferation of MGC-803 cells. So it may serve as a promising target in the treatment of gastric cancer.
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Objective To study the effect of metastasis-associated in colon cancer 1 ( MACC1 ) inhibition by small interference RNA( siRNA) on the formation of tumor cells that promote blood vessels, and to explore its possible molecular mechanism.Methods Synthesized MACC1 specific siRNA was transfected into human lung cancer cell lines XWLC-05. Then, the inhibitory effect of siRNA on the protein level of MET, MEK/p-MEK, ERK/p-ERK, and AKT/p-AKT was detected using Western blotting while the change in VEGF, bFGF and IL-8 protein level was detected using ELISA method. Results Western blotting results indicated that the expression level of MET, p-MEK and p-ERK was significantly decreased in the XWLC-05 cells transfected by MACC1 specific siRNA compared with control and nonsense siRNA groups, but the expression of total protein MEK and ERK did not change.Furthermore, the level of AKT and phosphorylated protein was not affected.ELISA results suggested that the secretion level of VEGF, bFGF and IL-8 was significantly suppressed at 48 h or 72 h compared with control and nonsense siRNA groups.Conclusion MACC1 may reduce the secretion levels of VEGF, bFGF and IL-8 via HGF/c-Met and MEK/ERK signal transduction pathways, and regulate angiogenesis of lung cancer.
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Recent findings indicate that metastasis-associated gene in colon cancer 1 ( MACC1 ) has an abnormal high expression in most malignant tumors.As a key regulator of HGF-MET signal pathway,MACC1 could obviously up-regulate the expression of MET and promote cancer cell's movement,invasion and metastasis.Further studies will shed light on elucidating the mechanisms of metastasis and may provide a new method for targeted therapy.