Down-regulation of EZH2 genes targeting RUNX3 affects proliferation, invasion, and metastasis of human colon cancer cells by Wnt/ß-catenin signaling pathway.

In order to detect the effect of EZH2 genes on proliferation, migration, invasion, and apoptosis of colon carcinoma cell strains HCT116 and HT29 by the Wnt/ß-catenin signaling pathway, qRT-PCR was applied to measure relative expressions of EZH2, RUNX3, CEA, CA199, MMP-9, VEGF, ß-catenin, and CyclinD1 in each group; Western-blot was employed with the intention of exploring relative expressions of these proteins in vivo and in vitro; monoclonal proliferation experiments and CCK-8 assay was adopted so as to check cell proliferation; the effect on cell migration was investigated via Transwell assay and cell scratch wound assay; flow cytometry was applied with a view to determining the effect on cell apoptosis. Transfected HCT116 cells are injected subcutaneously into nude mice. In colon cell strains HCT-116 and HT29, contrasted to the si-NC group, the RUNX3 expression was prominently up-regulated in the si-EZH2 group. Besides, expressions of CEA, CA199, MMP-9, and VEGF were significantly reduced; down-regulation of EZH2 genes remarkably inhibited cell proliferation, invasion and migration when facilitating apoptosis; down-regulation of EZH2 genes also significantly reduced expressions of essential proteins ß-catenin and CyclinD1 on the Wnt pathway. The subcutaneous tumor body of nude mice was reduced. EZH2-OE is the opposite trend to si-EZH2; The EZH2 gene may target regulatory RUNX3 regulation via that Wnt/ß-catenin signaling pathway, hence affecting colon carcinoma cell proliferation, invasion, migration, and apoptosis. Therefore, EZH2 may become a promising target for the clinical therapy of colon carcinoma.

Multidisciplinary approach to the diagnosis and treatment of patients with potentially resectable colorectal cancer liver metastasis: results of a multicenter study.

BACKGROUND: This study sought to review colorectal cancer liver metastasis (CRLM) patients at multiple centers to analyze the factors affecting the success of conversion therapy in patients whose CRLM was initially evaluated as potentially resectable, to explore the effect of different treatment approaches on patient survival, and to provide a scientific reference for clinical treatment of CRLM. METHODS: Fifty patients whose CRLM was initially evaluated as potentially resectable at 3 large Chinese general hospitals were enrolled in this retrospective study. Statistical analyses were carried out on the general data and pathological characteristic data to examine the clinical efficacy of the treatment approaches. The factors affecting the success of conversion therapy were analyzed by logistic regression. Additionally, follow-up appointments were conducted to examine survival, and survival curves were plotted using the Kaplan-Meier estimator. The effect of different clinical and pathological characteristics on CRLM patients was analyzed. RESULTS: Seventeen patients achieved no evidence of disease (NED) status through surgical resection/ablation after undergoing conversion therapy. The multifactor analysis demonstrated that the number of liver metastases was the primary risk factor affecting the efficacy of conversion therapy (P<0.05). Survival analysis results showed statistically significant difference in overall survival (OS) between the NED group and the inconspicuous/progressive group (P<0.0001). Also, there was a statistically significant difference in the progression-free survival (PFS) between the NED group and the inconspicuous/progressive group (P<0.0001). Patients in the surgical resection group had better OS and PFS than those in the ablation group (P<0.0001 and P<0.01, respectively). The monofactor analysis demonstrated that the number and maximum diameter of liver metastases, serum Carcino-Embryonic Antigen (CEA) level, and BRAF V600E mutation status were factors affecting the OS of CRLM patients (P<0.05), of which BRAF V600E mutation was the primary determinant (P<0.05). CONCLUSIONS: Among the patients whose CRLM was initially evaluated as unresectable, those who underwent surgical resection of the primary lesions and liver metastases after receiving conversion therapy had the best prognosis. Thus, a thorough evaluation should be conducted to determine the effect of and survival factors affecting conversion therapy in the treatment of liver metastases.