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Notch1, Jagged1, NF-κB and MMP-9 probably play a pivotal role during the CRC development, serving as biomarkers for early detection of the recurrence and metastasis and prognosis of CRC.

Background: Ethanol extracted from radix of Actinidia chinensis (EERAC) has been proved to be effective to inhibit colorectal cancer (CRC). Notch signaling pathway and angiogenesis in tumors are closely related with the progression of CRC. However, if EERAC could influence CRC through Notch signaling pathway and angiogenesis remains unclear. Methods: Flow cytometry, transwell, wound healing methods were used to measure cell apoptosis, invasion, migration, and proliferation. Protein and mRNA expression were detected using qRT-PCR and western blotting. Immunofluorescence staining was applied to detect the expression of target protein in the tissues. Results: The invasion, migration, and proliferation of CRC cells were remarkably suppressed by ERRAC. Significant promotion of cell apoptosis and cell ration in S stage were observed after EERAC treatment. The Notch1/DLL4/Hes1 signaling pathway and angiogenesis were suppressed by EERAC. Overexpression of LIM domain-binding 2 (LDB2) remarkably weakened the influence of ERRAC on the viability of CRC cells. Conclusions: EERAC might suppress CRC through targeting Notch/DLL4/Hes1 pathway and inhibiting angiogenesis in tumors. This study might provide novel thought for the prevention and therapy of CRC through targeting Notch/DLL4/Hes1.

Emerging evidence indicates that O(6)-methylguanine-DNA methyltransferase (MGMT) is a candidate for tumor suppression in several types of human tumors including colorectal cancer (CRC). However, the correlation between MGMT hypermethylation and clinicopathological characteristics of CRC remains unclear. In this study, we conducted a systematic review and meta-analysis to quantitatively evaluate the effects of MGMT hypermethylation on the incidence of CRC and clinicopathological characteristics. A comprehensive literature search was done from Web of Science, the Cochrane Library Database, PubMed, EMBASE, CINAHL, and the Chinese Biomedical Database for related research publications written in English and Chinese. Methodological quality of the studies was also evaluated. Analyses of pooled data were performed with Review Manager 5.2. Odds ratio (OR) and hazard ratio (HR) were calculated and summarized, respectively. Final analysis from 28 eligible studies was performed. MGMT hypermethylation is found to be significantly higher in CRC than in normal colorectal mucosa, the pooled OR from 13 studies including 1085 CRC and 899 normal colorectal mucosa, OR = 6.04, 95 % confidence interval (CI) = 4.69-7.77, p < 0.00001. MGMT hypermethylation is also significantly higher in colorectal adenoma than in normal colorectal mucosa, but it is significantly less compared to that in CRC patients. Interestingly, MGMT hypermethylation is correlated with sex status and is significantly higher in female than in male. MGMT hypermethylation is also associated with high levels of microsatellite instability (MSI). The pooled HR for overall survival (OS) shows that MGMT hypermethylation is not associated with worse survival in CRC patients. The results of this meta-analysis suggest that MGMT hypermethylation is associated with an increased risk and high levels of MSI and may play an important role in CRC initiation. However, MGMT hypermethylation may play an important role in the early stage of CRC progression and development, as well as having limited value in prediction of prognosis in CRC patients. We also discussed that MGMT may serve as a potential drug target of CRC.