ABSTRACT
ABSTRACT:Objective To investigate the effect of SDF-1/CXCR7 on inflammatory cytokine synthesis and secretion in gastric cancer SGC-7901 cells.Methods CXCR7 gene in SGC-7901 cells was silenced by shRNA lentiviral vector and the expression of CXCR7 was detected using Western blot and Real-time PCR.There were four groups as follows:LV-shRNA-NC,LV-shRNA-NC+SDF-1,LV-shRNA-CXCR7,and LV-shRNA-CXCR7+SDF-1 groups.Real-time PCR was used to detect the mRNA expressions of TNF-α,IL-1β,IL-6 and IL-8.ELISA was used to detect the protein levels of TNF-α,IL-1β,IL-6 and IL-8 in the culture supernatant.Western blot was used to detect the protein expressions of NF-κB pathway.Results ① Transfection of SGC-7901 cells with CXCR7-shRNA lentiviral vector resulted in a significantly decreased expression of CXCR7 at both mRNA and protein levels (all P<0.01).② Compared with those in LV-shRNA-NC group,IL-6 and IL-8 mRNA expressions and protein levels in the culture supernatant were increased in LV-shRNA-NC+SDF-1 group (P<0.01 )and decreased in LV-shRNA-CXCR7 group (P<0.05).Compared with those in LV-shRNA-NC+SDF-1 group,the expressions of IL-6 and IL-8 at mRNA and protein levels in the culture supernatant were significantly cut down in LV-shRNA-CXCR7+SDF-1 group (P<0.01 ).However,the expressions of TNF-αand IL-1βat mRNA and protein levels in the culture supernatant were not significantly changed by SDF-1 and CXCR7 shRNA.③ The protein expressions of nuclear NF-κB p65,t-IκBαand p-IκBαexhibited no significant differences among the four groups.Conclusion SDF-1/CXCR7 can promote the synthesis and secretion of inflammatory cytokines IL-6 and IL-8 in gastric cancer SGC-7 9 0 1 cells through an NF-κB-independent pathway.
ABSTRACT
Currently,a physiologically based pharmacokinetic(PBPK)model plays a key role in pharmaceutical research,which has been widely used at each stage of drug discovery and develop?ment. In the process of drug discovery,the selection of drug candidates is finished using the PBPK model to predict the pharmacokinetic properties of the drugs. In the process of preclinical development , through a combination of in vitro and physiological data amplification coefficient,the PBPK model can be used to predict not only the overall pharmacokinetic behavior of drug candidates in humans and animals and in vitro metabolism experiments,but also drug-drug interactions(DDI). In the course of clinical development,the PBPK model can help predict the difference between reference populations (age,different disease state,and polymorphism),especially the dosage and sampling time of the children. At present,the input parameters of PBPK model are mostly the mean values of the population,making it difficult to serve individuals. It is hoped that the input parameters of the model can reflect more of the individual characters according to the individual requirement,and that the time parameters of the input accord more with the actual physiological condition. In this article ,we briefly introduced the characteristics of common PBPK software,and reviewd the principle and feature of the PBPK model,as well as its application to drug discovery,preclinical development and clinical development,DDI,and individualized medication.