Establishment and comprehensive gene analysis of cells derived from 3-dimensional radial flow bioreactor culture system

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To establish of in vitro artificial organ model system for monitoring and evaluating the efficacy of medicine, usefulness of an original three dimensional culture system of radial flow type bioreactor (RFB) was examined using mainly biochemical determination in the drug responses. Under these conditions, the control of gene expressions such as drug metabolizing enzymes, drug resistance related- and apoptosis related-molecules was analyzed comprehensively from the result and a database of them was built. The liver cancer cells (FLC series) expressed CYP molecular species above the expectations by the three dimensional cultivation. On the other hand, the molecular species about the drug transportation and metabolism didn't change roughly. Moreover, the liver cancer cells increased the production of plasma proteins. By the three dimensional cultivation, the tumor cells controlled the expression of the cytoskeleton related-genes which are necessary for forming the three dimensional structure and the gene group which participates in the intercellular junction. A lot of gotten new-observations will make an intellectual property occur. When comparing the cellular drug-response of the FLC cells between a monolayer culture and a RFB cultivation, the cells cultured in RFB weakened the efficacy of the anticancer drug remarkably. The decline of the medicine effect was also confirmed in the treatment of the squamous cell carcinoma in the RFB cultivation. Now, it is analyzing the changes of the expressed genes. Because of the short term treatment of the liver cell cancer and the squamous cell carcinoma, the medicines affected mainly on the expression of stress-induced genes rather than that of genes of either drug-resistance or metabolism. Because the report is one with scarce field in the past, these results have an interest and are analyzed.Based on this result, we want to comprehensively analyze the gene expression which the RFB led and to make a database.