ABSTRACT
To explore the mechanism of β-carboline alkaloids inhibiting the migration and invasion of SGC-7901 cells and its correlation with FAK gene expression,CCK-8 method was used to determine the inhibitory rate of β-carboline alkaloids on the proliferation of gastric cancer SGC-7901 cells under different concentrations.The effect of β-carboline alkaloids on the migration and invasion of SGC-7901 cells was used by Transwell compartment.Detection of mRNA and protein expression of FAK genes were used by qRT-PCR and Western blot.Then si-FAK-1051 recombinant plasmid was transfected into SGC-7901 cells.FAK gene silencing effect was identified by qRT-PCR and Western blot technique again.Finally,the effects of FAK gene silencing on proliferation and migration of gastric cancer SGC-7901 cells were detected by CCK-8 kit and Transwell chamber assay respectively.With the increase of the concentration ofβ-carboline alkaloids,the inhibitory rate of SGC-7901 cells in human gastric cancer cells increased gradually,with IC5013.364 mg·L-1.The number of SGC-7901 cells of Transwell compartment in the positive experimental group(5-FU,5 mg·L-1) and the β-carboline alkaloids group decreased significantly(P<0.01) and the number of SGC-7901 cells in the β-carboline alkaloids group was significantly lower than that in the positive experimental group(P<0.01).Compared with the blank control group,the mRNA and protein expression level of FAK genes in the positive experimental group was significantly lower than that in the experimental group of β-carboline alkaloids(P<0.05).After transfection of si-FAK-1051 into gastric cancer SGC-7901 cells,the expression of mRNA and protein of FAK gene was significantly down regulated(P<0.05).SGC-7901 cell proliferation and cell migration ability also decreased significantly(P<0.05).β-carboline alkaloids are more effective than 5-FU in inhibiting migration and invasion of gastric cancer SGC-7901 cells,and the mechanism may be related to the inhibition of mRNA and protein expression of FAK gene by β-carboline alkaloids.
Subject(s)
Humans , Alkaloids , Pharmacology , Carbolines , Pharmacology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Focal Adhesion Kinase 1 , Genetics , Gene Expression Regulation, Neoplastic , Gene Silencing , Neoplasm Invasiveness , Stomach Neoplasms , Drug Therapy , PathologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the clinical phenotypes and hereditary patterns of the generalized epilepsy with febrile seizures plus (GEFS+).</p><p><b>METHODS</b>Detailed family trees were constructed by inquire and physical examinations for the probands of the 15 pedigrees of GEFS+. Some patients received electroencephalography, cranial CT or MRI examination. The seizures and epilepsy syndromes were classified according to the 2001 Seizure International Classification. The clinical data of GEFS+ were reviewed.</p><p><b>RESULTS</b>The 15 families consisted of 196 individuals. Seventy-five individuals were confirmed with epilepsy. The phenotypes of 64 out of the 75 patients with epilepsy conformed to GEFS+. The 64 patients included 38 males and 26 females (1 deceased) and there was no gender difference in the morbility of GEFS+. The age at onset was all in childhood. GEFS+ had a diversity of phenotypes. Febrile seizures (FS) were confirmed in 44 patients, FS and myoclonic seizure in 1, febrile seizures plus (FS+) in 13, FS+ and absence seizure in 2, FS+ and myoclonic seizure in 1, and FS+ and focal seizure in 3.</p><p><b>CONCLUSIONS</b>The heterogeneity of phenotypes and genetics may be the hallmarks of GEFS+. FS and FS+ are common phenotypes while FS+ and absence seizure, FS+ and myoclonic seizure, and FS+ and focal seizure are rare. If one of the parents is affected in a GEFS+ family, the susceptibility of their children to GEFS+ is the same no matter what gender of their children is. It is speculated that the hereditary pattern of GEFS+ conforms to autosomal dominant inheritance.</p>