Construction Of Hypoxia Enhanced Mitochondria-targeting MPG Expression System And Its Effects On Adenocarcinoma Multidrug Resistant Cell Line

Abnormality of apoptotic signal transmission is important mechanism for generation of mulidrug-resistance in cancer cells. There are many defects at pro-mitochondria level of apoptotic pathway in lung cancer multidrug resistant cells, so, targeting directly to mitochondria can avoid these defects. The characteristic of mitochondrial DNA(mtDNA), which is not protected by histones and presents a limited repair capacity, makes it an attractive target for pharmacological agents. To import the N-methylpurine-DNA glycosylase (MPG), which exist in nuclear originally, into mitochondria can lead the double strand breaks of mtDNA. Hypoxia, which differed from normal tissue, is the other important factor to influence the drug resistance of solid tumours, including lung cancer and also a distinguished characteristic. Hypoxia inducible factor (HIF), a kind of transcription factor, which existed in hypoxic environment, can be used as an enhancer to improve the specificity of target gene's expression. Therefore, basing on the observation of the relationship between hypoxia and drug resistance of A549/CDDP cells, hypoxia enhanced mitochondria-targeting MPG expression system will be constructed and it's effects on the biological character of A549/CDDP cells under hypoxia will be explored either.Objective1. To observe the effect of hypoxia on the drug resistance of pulmonary adenocarcinoma multidrug resistant cell line A549/CDDP, then to explore the possible mechanism for this phenomenon.2. To construct the hypoxia enhanced mitochondria-targeting MPG expression system and transfect it into A549/CDDP cells, then to investigate the biological characteristics of the tansfected cells under hypoxia after transfection. Materials and methods1. The 50% inhibitory concentration (IC50) for different drugs was determined by...