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Research on the mechanisms of docetaxel-resistant human lung adenocarcinoma
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Abstract:
In-depth study of the molecular mechanisms of lung adenocarcinoma resistance to docetaxel (DTX) not only offers us the new promising targets of individualized treatment for lung adenocarcinoma patients, but also provides new insights into clinical intervention strategies. In this study, the docetaxel-resistant human lung adenocarcinoma cell line SPC-A1/DTX was derived from parental SPC-A1 cell line by continuous exposure to increasing concentration of DTX in vitro. Differences in biological characteristics, such as cell morphology, chemosensitivity, cell proliferation, apoptosis, cell cycle, and drug transportation were compared between SPC-A1 and SPC-A1/DTX cell lines. Based on gene expression- and miRNA-microarray analysis, differentially expressed genes, such as ING4 and miRNAs (e.g. miR-200b and miR-100) were screened out from SPC-A1/DTX cells. With further gain-of-function and (or) loss-of-function studies of these molecules in both in vitro and in vivo models, we provided potential mechanistic explanations for DTX resistance of human lung adenocarcinoma. It was found that down-regulation of ING4 gene and abnormalities of crosstalk between miR-200b and E2F3gene and crosstalk between miR-100 and Plk-1gene might be essential for DTX resistance in human lung adenocarcinoma.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No.81071806, No. 81172106, No. 81272474)
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