The Study Of The Strategy Of 4HPR Combining With Anti-cancer Drugs And Key Brain Areas In Addiction

1. Mechanism study of 4HPR combining with anti-cancer and anti-inflammation drugs to synergistically induce tumor cell apoptosis. Fenretinide (4HPR) is a promising drug for cancer chemoprevention and chemotherapy which induce tumor cell apoptosis specifically and well tolerated. But it suggests new strategy in therapy because 4HPR has little effect on the recurrence and development of advanced tumor. 4HPR induces intracellur ROS(reactive oxygen species) and ER stress(Endoplasmic reticulum stress) to activate series of pathways including apoptosis pathway and anti-apoptosis pathways like NF-κB which mediates the development and progression of cancer, especially inflammation related cancer. Based on the known mechanism of 4HPR, we screen out Tetrandrine (Tet), which has synergistic effect with 4HPR in inducing apoptosis on tumor cells ,from some anti-cancer and anti-inflammation drugs. Tet is the main effective component of Stephenia tetrandra S Moore which has activities in anti-inflammation, anti-cancer, reversing MDR (multidrug resistance), blocking calcium ion channel and so on. Via in vitro experiments we find that 4HPR (4μM) and Tet (4-5μM) can inducing apoptosis synergistically on gastic and ovian tumor cell lines, and examine the expression of some important protein. According to the result we propose some possible mechanisms of the synergistic effect and provide foundation for further study. 2. Using genechip to analyse key brain areas in morphine-induced conditional preference place in rats. Drug addiction is defined as abnormal behavior with the characteristic of compulsive drug seeking behavior. Diffenrent brain areas reponse to addiction signal in area-specific way including constructure adaptaion in neurons and changes in physiological and biochemisty funcitions to pharmaceutical effect. The application of genechip is powerful in screening the the addiction related genes and underlying drug targets, but complexity of the structure and function of brain areas makes it hard to understand the gene expression and its function in different areas. Thus it is important to find the key brain area to study the circuit structure and gene's functions as well as the neurobiological foundation of drug addiction. And the application of genechip can alter the researchers to understand the changes in the brain areas during the addiction in the transcriptomic view. To find the key brain area in reward circuit in drug addiction, we use morphine induced conditional place preference model to determine rat that's easily to be induced in addiction or not and perform genechip experiments in the areas of nucleus accumbem, Amygdala, prefrontal cortex and hippocampus. After the analysis of the genechip data and validation of quantitative PCR, results suggest that nucleus accumbem and prefrontal cortex play more important roles. Our results provide foundation for the furthur study of the addiction related genes, new drug targets and addiction mechanism.