| Summary: | 碩士 === 輔仁大學 === 生命科學系碩士班 === 106 === As cancer treatment technology continues to thrive,chemical and radiational therapy are more sophisticated and diverse; however, these therapies accompany many side effects. Vascular endothelial dysfunction is one of these side effects. Chemotherapeutic drugs can cause many problems such as hypertension, renal failure and peripheral arterial disease, etc. Recently, many studies indicated that, ATP can increase energy absorption and delay the lethality of drugs, playing a very important role in cell protection. Based on the previous studies of our laboratory, ENERGI, a small molecular compound, has been shown to increase intracellular ATP content. In addition, ENERGI could relieve the toxic effects of anti-folate drugs (Aminopterin or Methotrexate) on human myeloid leukemia cells (K562 cell line). In this study, HUVEC and HAP1 cell lines were used as a cell model to investigate the energy metabolism pathways with drugs and to analyze the effects of different energy sources. When cells were co-treated with Chemotherapy drugs and ENERGI, the combined effects will increase cell survival rate and delay the lethality of chemotherapeutic drugs. This study can be categorized into two aspects. First, we found that ENERGI and Hypoxanthine could increase the ATP content inHUVEC cells and maintain the viability of cells with anti-folate chemotherapeutic drugs treatment (Methotrexate or Aminopterin). However, ENERGI and other purine compounds can not alleviate the cytotoxicity of Cis-platin, and then Guanine has been found to have negative effect on cells. Second, the influence of purine compounds with drugs in HAP1 wild type, HAP1 APRT, HAP1 PRPS1 and HAP1 HPRT knock out clones were analyzed. The results show that under the treatment of anti-folate drugs, ENERGI and Hypoxanthine can maintain the survival rate of HAP1 cells and increase the intracellular ATP content. However, under the same condition, we can’t get the same results in HAP1 APRT KO cell lines. However, ENERGI and Hypoxanthine can maintain the survival rate of HAP1 PRPS1 KO cell lines in the same treatment, but is poor than HAP1 WT. Finally, we found that Hypoxanthine has poor effects in HAP1 HPRT KO cell lines compared with HAP1 WT. Summary, ENERGI improve survival of cells under pressure and partially APRT involved; also Hypoxanthine to HPRT.
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