The Role Of ? Adrenergic Receptor In Regulating The Biological Behavior Of Non-small Cell Lung Cancer Cells

Lung cancer is one of the most common malignant tumors. Due to the lack of early diagnosis, prediction and effective treatment in patients with lung cancer, the five year survival rate is only 5%~15%. The main type of lung cancer is non small cell lung cancer(NSCLC), which accounts for about 80%~85% of lung cancer patients. It is very worthful for the research of novel therapeutic target by studying tumor biological characteristics and its mediated factors in NSCLC.?–Adrenoceptors(?-AR) are expressed in a variety of tumor cells and tissues including lung cancer cells. Research shows that, the pressure, pessimal stimulation and other factors can activate the sympathetic nervous-endocrine system, resulting in the increased release or secretion of epinephrine and noradrenalin. ?-AR overactivation can accelerate tumor development process. So far the relationship between adrenergic system and the occurrence and development of the NSCLC has been reported, hower, the function of ?–Adrenoceptors in the NSCLC cells apoptosis under the stress state of serum deprivation(hypoxia ischemia) and chemotherapeutic drugs cisplatin(gene damage) has not been reported.Meanwhile, the regulation of ?–Adrenoceptors for NSCLC growth in vivo and vitro has not yet been fully elucidated.In this study, RT-PCR, confocal, and Western blot were used to detect the expression of ?-adrenergic receptors. ELISA kit was applied to detect the level of intracellular and extracellular catecholamine released into the microenvironment from NSCLC. Western blot, flow cytometry and High content analysis were adopted to analyze the effects of ?-adrenergic receptors in apoptosis induced by serum deprivation or cisplatin, proliferation and EMT in NSCLC.Cell sphere formation experiment and subcutaneous transplantation technology were performed to detect the sphere formation ability and in vivo tumor growth.The results showed as following that A549?PC9?PC9-GR?H358 cell lines of NSCLC expressed ?1-AR, ?2-AR and ?3-AR. Activation of ?-AR had no obvious influence on EMT, proliferation and cancer stem cell survival of NSCLC cells but significantly reversed the apoptosis induced by serum deprivation in A549, PC9 cell line and reversed the apoptosis induced by cisplatin. Gene silencing or selectively blocked ?1-AR can alleviate the apoptosis reduced by serum deprivation, and the role of PI3 K signaling pathway was related. Besides, antagonist atenolol inhibited the growth of nude mice subcutaneously transplanted tumor and had the synergistic effect with cisplatin to inhibite tumor volumn. The study provides a certain value of experimental basis for the role of ?-AR in regulating the biological behavior of non-small cell lung cancer cells under stress state and potential application of selective antagonist of ?-AR.