The Effect Of Hyperbaric Oxygen Combined With Melatonin On Lung Adenocarcinoma A549 Cells And Their Possible Mechanisms

Background Lung Cancer is one of the deadliest cancers in both men and women.The most common type of lung cancer is adenocarcinoma;It is about 40 percent of all lung cancer.Compared with any other cancer,lung cancer causes more deaths in our country and needs to be constantly studied to seek new treatments.Tumor growth is limited by oxygen and nutrient delivery and waste removal.Tumor cells can survive by adapting to low oxygen conditions,which is a potential cause of recurrence and treatment failure of certain malignancies.So the new strategy for treating tumors is to change the low oxygen state of the tumor by increasing oxygenation,which may reverse or remove the tumor's adaptive defense or induce oxidative stress and promote tumor destruction.One way to improve the oxygenation of the tumor is to give hyperbaric oxygen.Hyperbaric Oxygen(HBO)treatment refers to the use of 100% Oxygen under high pressure.HBO has also been used in combination chemotherapy drugs to treat malignant tumors.This is based on the fact that HBO can make tumors more sensitive to radiotherapy and other forms of treatment by increasing the oxygen strain in the tumor.Melatonin(Melatonin MLT),is mainly composed of pineal indoles of synthesis and secretion of bioactive substances and has extensive biological activities,regulating biological rhythms,oxidation resistance,immunity,anti-aging,analgesia,sedation,and so on.In addition to the above physiological effects,MLT also has an obvious role in preventing,treating tumors and delaying tumor progression.The role of MLT in patients with lung cancer has been reported.This topic selection of A549 lung cancer cells as an in vitro model,explore MLT and HBO combined MLT influence on the cell biology behavior,the results will provide hyperbaric oxygen as an aid in the treatment of tumor therapy provides reliable theoretical basis,to improve the prognosis of patients with clinical tumor provides effective treatment option.Aim To study the effects of HBO combined MLT on proliferation,differentiation,metastasis and apoptosis of lung adenocarcinoma cell A549,and to explore its possible mechanism.Methods The lung adenocarcinoma cell line A549 was treated with HBO united MLT.Determined by MTT method to detect HBO combined MLT on A549 cell proliferation inhibition,with Hoechst staining and flow cytometry to detect HBO combined MLT influence on A549 cell differentiation and apoptosis,scratch test HBO combined MLT effect on A549 cell invasion and metastasis ability.Western blot method was used to detect the influence of HBO united MLT on expression of bcl-2 / Bax,and GRP78 / CHOP of the related protein of endoplasmic reticulum.Western blot detection joint MLT HBO treatment on A549 cells and tumor cell differentiation,proliferation,invasion,metastasis and its signal transduction protein MMP-9,endocan,P53,PTPRB,Src phosphorylation level and the influence of HIF-1? expression.Results Melatonin can inhibit lung adenocarcinoma A549 cell proliferation,and can increase the expression of tumor suppressor gene p53,melatonin combined hyperbaric oxygen treatment A549 cell,tumor suppressor gene p53 expression is significantly higher than individual melatonin group,its proliferation ability decline further.Melatonin can inhibit lung adenocarcinoma A549 cell migration,and the ability to inhibit the expression of MMP-9,melatonin combined hyperbaric oxygen treatment A549 cells,the expression of MMP-9 was lower than that in group of melatonin alone,its ability to migrate down further.Melatonin can be used to induce the differentiation of adenocarcinoma A549 cells and inhibit the expression of endocan,while the expression of endocan is significantly lower in the treatment of A549 cells by melatonin combined with hyperbaric oxygen treatment.Melatonin can induce apoptosis of lung adenocarcinoma A549 cells,and can be cut in the expression of apoptosis inhibiting protein the Bcl-2 and CHOP,promote Bax apoptosis protein,the expression of GRP78,raised melatonin combined hyperbaric oxygen treatment A549 cell,cell apoptosis significantly stronger than melatonin groups separately.Melatonin can inhibit lung adenocarcinoma A549 cells,and can inhibit HIF-1?expression,melatonin combined hyperbaric oxygen treatment A549 cell,HIF-1? expression was lower than that in group of melatonin alone,its ability to attack down further.Melatonin combined hyperbaric oxygen can increase the expression of lung adenocarcinoma A549 cells PTPRB,mechanism may be related to melatonin combined hyperbaric oxygen can inhibit the Src phosphorylation levels,and the expression of PTPRB lung adenocarcinoma A549 cell proliferation significantly reduced.Conclusions Melatonin inhibits the proliferation and migration of adenocarcinoma A549 cells,induces its differentiation,promotes its apoptosis and other mechanisms to play an anti-tumor role,and hyperbaric oxygen can enhance the anti-tumor effect of melatonin.The mechanism of melatonin combined with hyperbaric oxygen for adenocarcinoma of lung adenocarcinoma was related to the regulation of apoptosis related genes,angiogenesis related genes and the expression of certain tumor suppressor genes.