@article { author = {Sae-lim, Suvaraporn and Soontornworajit, Boonchoy and Rotkrua, Pichayanoot}, title = {Inhibition of Colorectal Cancer Cell Proliferation by Regulating Platelet-Derived Growth Factor B Signaling with a DNA Aptamer}, journal = {Asian Pacific Journal of Cancer Prevention}, volume = {20}, number = {2}, pages = {487-494}, year = {2019}, publisher = {West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter.}, issn = {1513-7368}, eissn = {2476-762X}, doi = {10.31557/APJCP.2019.20.2.487}, abstract = {Background: Overexpression of platelet-derived growth factor-BB (PDGF-BB) is associated with colorectalcarcinogenesis. PDGF-BB plays a role in the autocrine growth stimulation of cancer cells. Aptamers are shortsingle-stranded oligonucleotides that can bind to cellular targets with high affinity and specificity and offer the advantageof non-immunogenicity, non-toxicity and high stability. Thus, they receive interest as potential therapeutic agents.Methods: The endogenous level of PDGF-BB in Caco-2 and SW480, colorectal cancer (CRC) cells, was evaluatedusing ELISA. The effect of the PDGF-BB aptamer on cell proliferation was investigated in two CRC cell lines andCCD841 CoN, normal colon cells. The effective molar ratio between PDGF-BB and PDGF-BB aptamer was furtherexplored. Cell viability in all experiments was analyzed using MTS assay. Western blotting was performed to examinethe alteration of relevant signaling pathways. Results: Caco-2 and SW480 cells endogenously synthesized and secretedPDGF-BB to stimulate their growth. Cells treated with the PDGF-BB aptamer proliferated at a slower rate, but CCD841CoN did not. Pre-incubation of PDGF-BB with the corresponding aptamer at the molar ratio 1:1 could significantlysilence its proliferative effect on CRC cells. Western blot analysis revealed that the phosphorylation level of ERK1/2, akey component in PDGF downstream signaling pathway, was down-regulated by the aptamer, indicating the underlyingmechanism of inhibition of CRC cell proliferation. Conclusions: This study demonstrated that using a DNA aptamerto interfere with the binding of PDGF-BB to its receptor suppressed CRC cell proliferation in part via down-regulationof the Ras/Raf/MEK/ERK signaling pathway. It raised the possibility that the PDGF-BB-specific aptamer could be apromising therapeutic agent for CRC targeted therapy.}, keywords = {colorectal cancer,DNA aptamer,ERK1/2,platelet-derived growth factor B}, url = {https://journal.waocp.org/article_82408.html}, eprint = {https://journal.waocp.org/article_82408_7e3a338403d0ab88b16f62853a6e6dac.pdf} }