Dermaseptin B2’s Anti-Proliferative Activity and down Regulation of Anti-Proliferative, Angiogenic and Metastatic Genes in Rhabdomyosarcoma RD Cells in Vitro
Loading...
Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Advances in Bioscience and Biotechnology
Abstract
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.
Aim: Evaluating the in vitro anti-proliferative activity of Dermaseptin
B2 on Rhabdomyosarcoma RD (CCL-136TM) cells and its effect on the
expression of MYC, FGFR1, NOTCH1, and CXCR7 genes involve in processes
including proliferation, angiogenesis and metastasis. Methods: 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 MYC, NOTCH1, FGFR1 and CXCR7, total RNA was extracted from the
cells and q-RT-PCR was performed with β-Actin as reference gene. Results:
Dermaseptin B2 inhibited the proliferation of RD cells in a time and concentration
dependent manner as with IC50 values of 7.679 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 MYC (fc; 1.5013, 1.5185, 2.4144), CXCR7 (fc; 2.8818, 4.4430, 3.9924), FGFR1 (fc; 2.3515, 2.0809, 2.2543), NOTCH1 (fc; 2.4667, 4.6274, 4.3352)
genes for the three-time points respectively. NOTCH1 and CXCR7 showed
higher fold changes with respect to β-Actin than MYC and FGFR1. Conclusion:
The results of this study indicate that Dermaseptin B2 is a target molecule
for signaling pathways including PI3K/AKT, RTK and NOTCH pathways
that could affect the transcription of these genes and overall inhibition
of cancer progression. Further studies are needed to give a better understanding
of the detailed mechanisms of action as well as the effects of the
Dermaseptin B2 peptide in vivo.
Description
Keywords
Dermaseptin B2, Doxorubicin, RMS, Angiogenesis, Metastasis
Citation
Abdille, A.A., Kimani, J., Wamunyokoli, F., Bulimo, W., Gavamukulya, Y. and Maina, E.N. (2021) Dermaseptin B2’s Anti-Proliferative Activity and down Regulation of Anti-Proliferative, Angiogenic and Metastatic Genes in Rhabdomyosarcoma RD Cells in Vitro. Advances in Bioscience and Biotechnology, 12, 337-359. https://doi.org/10.4236/abb.2021.1210022