NF-B, E-cadherin and Fas regulate the proliferation, invasion and migration of CRC cells

NF-B, E-cadherin and Fas regulate the proliferation, invasion and migration of CRC cells. Fas, Fas-associated via loss of life area (FADD), caspase-8, caspase-3, matrix metalloproteinase (MMP)-9, nuclear aspect (NF)-B, Claudin-3 and E-cadherin had been discovered using quantitative PCR evaluation, zymography and traditional western blotting. The outcomes uncovered that curcumin markedly inhibited the viability and proliferation of HCT-116 cells within a dosage- and time-dependent way. The migration, aggregation and invasion of HCT-116 cells in to the lungs of mice had been reduced by curcumin treatment within a dose-dependent way. S-phase arrest and steadily increased apoptotic prices of HCT-116 cells had been observed with raising curcumin concentrations. Additionally, the mRNA and protein degrees of apoptosis-associated proteins (Fas, FADD, caspase-8 PKR-IN-2 and caspase-3) and E-cadherin in HCT-116 cells had been upregulated pursuing treatment with curcumin within a dose-dependent way. In comparison, the appearance of migration-associated proteins, including MMP-9, Claudin-3 and NF-B, was downregulated with raising curcumin concentrations. These data suggested the fact that inhibitory aftereffect of curcumin in HCT-116 cells might match that of 5-FU. As a result, curcumin induced cell apoptosis and inhibited tumor cell metastasis by regulating the NF-B signaling pathway, and its own therapeutic impact may be much like that of 5-FU. (9) had been the first ever to propose the usage of curcumin in the treating tumors. Subsequently, a lot of research (8,10) confirmed that curcumin may possess anti-infection, anti-inflammatory, tumor and antioxidant development inhibitory properties. Curcumin continues to be known as a third-generation anticancer medication because of its wide anticancer range, high performance and low toxicity (10). Cell apoptosis, also called designed cell loss of life, is an essential process for cells to maintain life activities. Cysteinyl aspartate-specific proteinases (caspases) are a group of proteins that play a key role in promoting apoptosis (11). There are three classical signaling pathways that can induce cancer cell apoptosis: The death receptor, mitochondrial and endoplasmic reticulum signaling pathways (12). Fas receptor-mediated apoptosis is one of the most important death receptor signaling pathways. The cancer stem cell theory of tumor growth suggests that Fas signaling may be involved in cell apoptosis, cell senescence and tumor maintenance (13). The malignant degree of CRC is determined by hematogenous and lymphatic metastasis, as well as local invasion. The pathogenesis of CRC is currently a clinical research focus. It has been reported that epithelial-to-mesenchymal transition (EMT) is crucial for the development and progression of malignant tumors, mainly manifesting as the disruption of the tight connections between marginal tumor cells (14). Additionally, claudin and matrix metalloproteinase (MMP) protein regulation is associated with tumor metastasis (15,16). The activation of the nuclear factor (NF)-B signaling pathway promotes the transcription of inflammatory factors, chemokines, adhesion molecules and growth factor-related genes, thus leading to tumor development (17), and it may represent an effective antitumor strategy for inducing tumor cell apoptosis and inhibiting tumor cell activity and invasion. The aim PKR-IN-2 of the present study was to investigate the antitumor effects of curcumin on CRC cell proliferation, migration and apoptosis, explore the possible underlying molecular mechanisms, and compare the antitumor efficacy of curcumin with that of 5-FU, PKR-IN-2 in order to determine whether curcumin may be considered as a potential drug for the treatment of patients with CRC. Materials and methods Cells and animals The HCT-116 cell line was purchased from the China Center for Type Culture Collection. The cells were maintained in RPMI-1640 medium (HyClone; Cytiva) supplemented with 10% FBS (Hangzhou Sijiqing Biological Engineering Materials Co., Ltd.) and antibiotics (100 U/ml streptomycin and 100 U/ml penicillin) in an incubator at 37C with 5% Co2. A total of 24 Kunming mice, aged 4 weeks and weighing 202 g, were purchased from the Hubei Provincial Center for Disease Control and Prevention. The mice were housed at room temperature with 45C55% humidity and with a 10/14-h light/dark cycle under pathogen-free conditions. The health status of the mice was monitored daily. The humane endpoints were deterioration of their general condition, and the mice were sacrificed in the event of a body weight loss of >20%. All animal protocols were approved by the Hubei University of Traditional Chinese Medicine Ethics Committee. Cell experimental groups The following CAB39L five treatment groups were used in the experiments: Control (no curcumin or 5-FU); CUR(L).

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