Dermaseptin B2’s Anti-Proliferative Activity and down Regulation of Anti-Proliferative, Angiogenic and Metastatic Genes in Rhabdomyosarcoma RD Cells <i>in Vitro</i>  

作　　者：Ahmed A. Abdille Josephine Kimani Fred Wamunyokoli Wallace Bulimo Yahaya Gavamukulya Esther N. Maina Ahmed A. Abdille;Josephine Kimani;Fred Wamunyokoli;Wallace Bulimo;Yahaya Gavamukulya;Esther N. Maina(Department of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences Technology and Innovation (PAUSTI), Nairobi, Kenya;Department of Biochemistry, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya;Centre for Public Health Research, Kenya Medical Research Institute, Nairobi, Kenya;Department of Biochemistry and Molecular Biology, Faculty of Health Sciences, Busitema University, Mbale, Uganda;Department of Biochemistry, College of Health Sciences, University of Nairobi, Nairobi, Kenya)

机构地区：[1]Department of Molecular Biology and Biotechnology, Pan African University Institute for Basic Sciences Technology and Innovation (PAUSTI), Nairobi, Kenya [2]Department of Biochemistry, College of Health Sciences, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya [3]Centre for Public Health Research, Kenya Medical Research Institute, Nairobi, Kenya [4]Department of Biochemistry and Molecular Biology, Faculty of Health Sciences, Busitema University, Mbale, Uganda [5]Department of Biochemistry, College of Health Sciences, University of Nairobi, Nairobi, Kenya

出　　处：《Advances in Bioscience and Biotechnology》2021年第10期337-359,共23页生命科学与技术进展（英文）

摘　　要：<b><span style="font-family:"">Background: </span></b><span style="font-family:"">Rhabdomyosarcoma (RMS) is the most prevalent soft tissue sarcoma in children, representing approximately 50% of pediatric sarcomas and can develop in any part of the body though more frequently at the extremities. <b>Aim: </b>Evaluating the<i> in vitro</i> anti-proliferative activity of Dermaseptin B2 on Rhabdomyosarcoma RD (CCL-136TM) cells and its effect on the <span>expression of <i>MYC, FGFR1, NOTCH1</i>, and CXCR7 genes involve in processes </span>including proliferation, angiogenesis and metastasis. <b>Methods: </b>RD cells were grown in Dulbecco’s Modified Eagle’s Medium supplemented with 10% Fetal Bovine Serum. Exponentially growing cells were treated with Dermaseptin B2 and Antiproliferative activity was assayed using the resazurin and migration assays at three time-points. In order to determine the gene expression profiles of <i>MYC, NOTCH1, FGFR1 </i>and<i> CXCR7</i>, total RNA was extracted from the cells and q-RT-PCR was performed with <i>β-Actin</i> as reference gene. <b>Results: </b>Dermaseptin B2 inhibited the proliferation of RD cells in a time and concentration dependent manner as with IC₅₀ values of 7.679</span><span style="font-family:""> </span><span style="font-family:"">μM, 7.235 μM, 5.993 μM. The 2-dimentional wound healing assay showed inhibition of migration and motility of the RD cells at time-points of 6, 24, 48 and 72-hours with the greatest inhibition observed at 72-hours. Dermaseptin B2 downregulated the target <i>MYC</i> (fc;1.5013, 1.5185, 2.4144), <i>CXCR7</i> (fc;2.8818, 4.4430, 3.9924), <i>FGFR1</i> (fc;2.3515, 2.0809, 2.2543), <i>NOTCH1</i> (fc;2.4667, 4.6274, 4.3352) genes for the three-time points respectively. <i>NOTCH1</i> and <i>CXCR7</i> showed higher fold changes with respect to <i>β-Actin</i> than <i>MYC</i> and <i>FGFR1</i>. <b>Conclusion: </b>The results of this study indicate that Dermaseptin B2 </span><span style="font-family:"">is</span><span style="font-family:""<b><span style="font-family:"">Background: </span></b><span style="font-family:"">Rhabdomyosarcoma (RMS) is the most prevalent soft tissue sarcoma in children, representing approximately 50% of pediatric sarcomas and can develop in any part of the body though more frequently at the extremities. <b>Aim: </b>Evaluating the<i> in vitro</i> anti-proliferative activity of Dermaseptin B2 on Rhabdomyosarcoma RD (CCL-136TM) cells and its effect on the <span>expression of <i>MYC, FGFR1, NOTCH1</i>, and CXCR7 genes involve in processes </span>including proliferation, angiogenesis and metastasis. <b>Methods: </b>RD cells were grown in Dulbecco’s Modified Eagle’s Medium supplemented with 10% Fetal Bovine Serum. Exponentially growing cells were treated with Dermaseptin B2 and Antiproliferative activity was assayed using the resazurin and migration assays at three time-points. In order to determine the gene expression profiles of <i>MYC, NOTCH1, FGFR1 </i>and<i> CXCR7</i>, total RNA was extracted from the cells and q-RT-PCR was performed with <i>β-Actin</i> as reference gene. <b>Results: </b>Dermaseptin B2 inhibited the proliferation of RD cells in a time and concentration dependent manner as with IC₅₀ values of 7.679</span><span style="font-family:""> </span><span style="font-family:"">μM, 7.235 μM, 5.993 μM. The 2-dimentional wound healing assay showed inhibition of migration and motility of the RD cells at time-points of 6, 24, 48 and 72-hours with the greatest inhibition observed at 72-hours. Dermaseptin B2 downregulated the target <i>MYC</i> (fc;1.5013, 1.5185, 2.4144), <i>CXCR7</i> (fc;2.8818, 4.4430, 3.9924), <i>FGFR1</i> (fc;2.3515, 2.0809, 2.2543), <i>NOTCH1</i> (fc;2.4667, 4.6274, 4.3352) genes for the three-time points respectively. <i>NOTCH1</i> and <i>CXCR7</i> showed higher fold changes with respect to <i>β-Actin</i> than <i>MYC</i> and <i>FGFR1</i>. <b>Conclusion: </b>The results of this study indicate that Dermaseptin B2 </span><span style="font-family:"">is</span><span style="font-family:""

关 键 词：Dermaseptin B2 Doxorubicin RMS Angiogenesis Metastasis 

分 类 号：R73[医药卫生—肿瘤]