Chemosensitivity Effects And Mitochondria Mechanisms Study On The Human Lung Adenocarcinoma Cell Line A549

ObjectiveCisplatin (CDDP) is one of the commonly used and effective drugs in treating adenocarcinoma of lung. The previous investigation indicated that ultra-activation of mitochondrial oxidative phosphorization function induced by CDDP positively participated in the process of CDDP related resistance in lung adenocarcinoma cells. Chloramphenicol (CAP) is one of the protein synthesis inhibitors of mitochondria. It can inhibit the function of mitochondria and induce apoptosis. The anticancer activity mechanism of artemether (ARE) is related with the structure damage of mitochondrial DNA(mtDNA) and the function disorder of mitochondria. It is very important to study the chemosensitivity effects and the mitochondrial mechanisms of CDDP combination with CAP and ARE respectively on the lung adenocarcinoma cells.MethodsStudy the anticancer activity in different concentration of CAP and ARE on human lung adenocarcinoma cells line A549,and the effects of combination of CDDP and CAP or ARE respectively. Cell proliferation was evaluated by MTT assay. The 50% inhibited concentration (Dm) of each drug was calculated by the median-effect principle. Apoptotic rate was determined by flow cytometry (FCM). The morphologic and structural changes of A549 cell were observed by transmission electron microscope (TEM). ATP was detected by ATP Assay Kit at different time after giving different drugs. Gene expression of mitochondrial genome was analyzed based on the results. After giving CDDP+CAP and CDDP+ARE on A549 cells for 24 and 48 hours. Total RNA was extracted from remained cancer cells respectively. Then the differential expressions of mtDNA genes were detected with the mtDNA oligonucleotide microarray.