Gene expression patterns induced by taxol(R) and cyclosporin a in oral squamous cell carcinoma cell line using cDNA microarray

Kim, Yong Kwan; Lee, Jae Hoon; Kim, Chul Hwan

Abstract

It is well-known that paclitaxel(Taxol(R)), which is extracted from the pacific and English yew, has been used as a chemotherapeutic agent for ovarian carcinoma and advanced breast carcinoma and Cyclosporin A, which is highly lipophilic cyclic peptide and isolated from a fungus, has been also used as an useful immunosuppressive drug after transplantation and is associated with cellular apoptosis. Since 1953, in which James Watson, Rosalind Franklin and Francis Crick discovered the double helical structure of DNA, a few kinds of techniques for identifying gene expression have been developed. In postgenomic period, many of researchers have used the DNA microarray which is high throughput screening technique to screen large numbers of gene expression simultaneously. In this study, we searched and screened the gene expression in the oral squamous cell carcinoma cell lines treated with Taxol(R), cyclosporin or cyclosporin combined with Taxol(R) using cDNA microarray. The results were as following; 1. It was useful that the appropriate concentration of Cyclosporin A and Taxol(R) used in oral squamous cell carcinoma cell line was under 1 microgram/ml and 3 microgram/ml. 2. In the experimental group in which Taxol(R) and Taxol(R) + Cyclosporin A were used, the cell growth was extremely decreased. 3. In the group in which Cyclosporin A was used, the MTT assay was rarely decreased which means the activity of succinyl dehydrogenase is remained in mitochondria but in the group in which the mixture of Cyclosporin A and Taxol(R) were used, the MTT assay was extremely decreased. 4. In the each group in which Cyclosporin A(3 microgram/ml) and Taxol(R)(1 microgram/ml) were used, the cell arrest was appeared in G2/M phase and in the group in which Taxol(R)(3 microgram/ml) was used, the cell arrest was appeared in both S phase and G2/M phase. 5. In the oral squamous cell carcinoma cell line treated with Taxol(R), several genes including ANGPTL4, RALBP1 and TXNRD1, associated with apoptosis, SUI1, MAC30, RRAGA and CTGF, related with cell growth, HUS1 and DUSP5, related with cell cycle and proliferation, ATF4 and CEBPG, associated with transcription factor, BTG1 and VEGF, associated with angiogenesis, FDPS, FCER1G, GPA33 and EPHA4 associated with signal transduction and receptor activity and AKR1C2 and UGTA10 related with carcinogenesis were detected in increased levels. The genes that showed increaced expression in the oral squamous cell carcinoma cell line treated with Cyclosporin A were CYR61, SERPINB2, SSR3 and UPA3A which are known as genes associated with cell growth, carcinogenesis, receptor activity and transcription factor. The genes expressed in the HN22 cell line treated with cyclosporin combined with Taxol(R) were ALCAM and GTSE1 associated with cancer invasiveness and cell cycle regulation.