The effect of chemotherapy drugs on the regulation of drug resistance genes

• Main Authors: Ming-Jou Lu, 呂明柔
• Other Authors: Cheng-Nan Chen
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/877dq7

碩士 === 國立嘉義大學 === 生化科技學系研究所 === 105 === Renal cell carcinoma and glioblastoma multiform are very poor prognostic effects of cancer. In clinical treatment, cast chemotherapy drugs, surgery and radiation therapy is the main treatment of renal cell carcinoma and multinucleated neuroblastoma in the way. But the renal cell carcinoma was found in the patient when most of them into the end of cancer, and polymorphic neuroblastoma itself is highly deteriorated cancer, with a high degree of metastasis ability; both for their first-line chemotherapy drugs sorafenib ( Treatment of renal cell carcinoma) and temozolomide (treatment of polymorphic neuroblastoma) is easy to produce drug resistance, the main goal of this experiment to explore whether the performance of DNA repair genes caused by cancer cells with drug resistance. Renal cell carcinoma cells used in this study are 786-O cell lines, while the glioblastoma multiform is the U87 cell line. First, cell survival was analyzed cell viability after drug. After selecting the appropriate drug concentration, the mRNA expression of the DNA repair gene was analyzed for the samples collected at different time points. The target genes for the DNA repair gene were XRCC1, MSH2 and Rad51, XRCC1 is one of the proteins of the base excision repair(BER),MSH2 is a protein member in DNA mismatch repair system(MMR), and Rad51 is a member of the recombination repair system. Subsequent addition of inhibitors of different pathways, trying to analyze DNA repair genes and those pathways may be relevant. Finally, it is observed whether the protein expression of the DNA repair gene and the expression of the protein in the relevant path are consistent with the mRNA expression. According to the experimental results, 786-O treatment of sorafenib, XRCC1 mRNA expression at 8H to about 1.7 times, and XRCC1 expression is related to PI3K / Akt path. While the U87 cell line in the dosing treatment Temozolomide, it is at 72H Rad51 3.4 times the mRNA expression. The above does not rule out that 786-O, if treated at a lower concentration of Sorafenib, and elongated the time of collection of the sample, may have the opportunity to observe an increase in the mRNA expression of Rad51 and to compare the performance of different repair genes at different time points Quantity and possible path differences.