ABSTRACT
The effects of oenothein B(OEB) on the proliferation, apoptosis, invasion, and migration of breast cancer MCF-7 and MDA-MB-231 cells were investigated by cell culture in vitro, network pharmacology, and molecular docking. In vitro cell experiments revealed that OEB inhibited the proliferation and colony formation ability, and promoted the apoptosis and formation of apoptotic bodies in breast cancer cells, as well as inhibited the invasion and migration of breast cancer cells. The targets of OEB were obtained using SwissTargetPrediction database and breast cancer targets were obtained from GeneCards. The targets of OEB and breast cancer were entered separately in Venny 2.1 software to obtain the Venn diagram of common targets of OEB and breast cancer. The common targets of OEB and breast cancer were input into STRING database to construct a protein-protein interaction(PPI) network, which was entered into Cytoscape 3.7.2 software for network topology analysis. Key targets were screened according to protein association strength, and analyzed for KEGG pathway enrichment. Molecular docking of OEB to key targets using AutoDock software revealed that OEB stably bound to the active pocket of P53, while OEB promoted the expression of P53 protein. MCF-7 and MDA-MB-231 cell viability and migration ability increased after silencing P53, and this change was reversed after treatment with OEB. Therefore, this study showed that OEB inhibited the proliferation, migration, and invasion of breast cancer MCF-7 and MDA-MB-231 cells, and promoted the apoptosis of breast cancer MCF-7 and MDA-MB-231 cells, which may be related to the targeted regulation of P53.
Subject(s)
Breast Neoplasms , Humans , Female , Cell Proliferation , Breast Neoplasms/drug therapy , Tumor Suppressor Protein p53/genetics , Molecular Docking SimulationABSTRACT
AIM: To analyze the frequency of hereditary non-polyposis colorectal cancer (HNPCC) in Chinese colorectal cancer (CRC) patients, and to discuss the value of microsatellite instability (MSI) and/or immunohistochemistry (IHC) for MSH2/MLH1 protein analysis as pre-screening tests in China. METHODS: The Amsterdam criteria I and II (clinical diagnosis) and/or germline hMLH1/hMSH2 mutations (genetic diagnosis) were used to classify HNPCC families. Genetic tests, including microsatellite instability, immunohistochemistry for MSH2/MLH1 proteins and hMSH2/hMLH1 genes, were performed in each proband. RESULTS: From July 2000 to June 2004, 1988 patients with colorectal cancer were analysed and 114 CRC patients (5.7%) from 48 families were categorized as having HNPCC, including 76 from 26 families diagnosed clinically and 38 from the other 22 families diagnosed genetically. The sensitivity and specificity of high MSI and IHC for predicting mutations were 100% and 54%, and 79% and 77%, respectively. CONCLUSION: The frequency of HNPCC is approximately 10% among all Chinese CRC cases. The MSI and IHC detections for hMSH2/hMLH1 proteins are reliable pre-screening tests for hMLH1/hMSH2 germline mutations in families suspected of having HNPCC.
Subject(s)
Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/genetics , Adaptor Proteins, Signal Transducing , Carrier Proteins/genetics , China/epidemiology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/ethnology , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/ethnology , DNA, Neoplasm/genetics , Gene Expression Regulation, Neoplastic , Genetic Testing/methods , Germ-Line Mutation/genetics , Guidelines as Topic , Humans , Incidence , Microsatellite Instability , MutL Protein Homolog 1 , MutS Homolog 2 Protein/genetics , Nuclear Proteins/genetics , Prospective Studies , Sensitivity and SpecificityABSTRACT
AIM: To determine the efficacy and long-term outcome of biofeedback treatment for chronic idiopathic constipation and to compare the efficacy of two modes of biofeedback (EMG-based and manometry-based biofeedback). METHODS: Fifty consecutive contactable patients included 8 cases of slow transit constipation, 36 cases of anorectic outlet obstruction and 6 cases of mixed constipation. Two modes of biofeedback were used for these 50 patients, 30 of whom had EMG-based biofeedback, and 20 had manometry-based biofeedback. Before treatment, a consultation and physical examination were done for all the patients, related information such as bowel function and gut transit time was documented, psychological test (symptom checklist 90, SCL90) and anorectic physiological test and defecography were applied. After biofeedback management, all the patients were followed up. The Student's t-test, chi-squared test and Logistic regression were used for statistical analysis. RESULTS: The period of following up ranged from 12 to 24 months (Median 18 months). 70 % of patients felt that biofeedback was helpful, and 62.5 % of patients with constipation were improved. Clinical manifestations including straining, abdominal pain, bloating, were relieved, and less oral laxative was used. Spontaneous bowel frequency and psychological state were improved significantly after treatment. Patients with slow and normal transit, and those with and without paradoxical contraction of the anal sphincter on straining, benefited equally from the treatment. The psychological status rather than anorectal test could predict outcome. The efficacy of the two modes of biofeedback was similar without side effects. CONCLUSION: This study suggests that biofeedback has a long-term effect with no side effects, for the majority of patients with chronic idiopathic constipation unresponsive to traditional treatment. Pelvic floor abnormalities and transit time should not be the selection criteria for treatment.