Abstract
Background:Overexpression of platelet-derived growth factor-BB (PDGF-BB) is associated with colorectal carcinogenesis. PDGF-BB plays a role in the autocrine growth stimulation of cancer cells. Aptamers are short single-stranded oligonucleotides that can bind to cellular targets with high affinity and specificity and offer the advantage of 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 evaluated using ELISA. The effect of the PDGF-BB aptamer on cell proliferation was investigated in two CRC cell lines and CCD841 CoN, normal colon cells. The effective molar ratio between PDGF-BB and PDGF-BB aptamer was further explored. Cell viability in all experiments was analyzed using MTS assay. Western blotting was performed to examine the alteration of relevant signaling pathways. Results:Caco-2 and SW480 cells endogenously synthesized and secreted PDGF-BB to stimulate their growth. Cells treated with the PDGF-BB aptamer proliferated at a slower rate, but CCD841 CoN did not. Pre-incubation of PDGF-BB with the corresponding aptamer at the molar ratio 1:1 could significantly silence its proliferative effect on CRC cells. Western blot analysis revealed that the phosphorylation level of ERK1/2, a key component in PDGF downstream signaling pathway, was down-regulated by the aptamer, indicating the underlying mechanism of inhibition of CRC cell proliferation. Conclusions:This study demonstrated that using a DNA aptamer to interfere with the binding of PDGF-BB to its receptor suppressed CRC cell proliferation in part via down-regulation of the Ras/Raf/MEK/ERK signaling pathway. It raised the possibility that the PDGF-BB-specific aptamer could be a promising therapeutic agent for CRC targeted therapy.
Highlights
Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women worldwide (Ferlay et al, 2013)
This study demonstrated that using a DNA aptamer to interfere with the binding of platelet-derived growth factor-BB (PDGF-BB) to its receptor suppressed colorectal cancer (CRC) cell proliferation in part via down-regulation of the Ras/Raf/MEK/ERK signaling pathway
We found that PDGF-BB was endogenously produced and secreted by CRC cell lines: Caco-2 and SW480
Summary
Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women worldwide (Ferlay et al, 2013). Platelet-derived growth factors (PDGFs) are the targets of interest because they play important roles in cancer cell growth, angiogenesis and metastasis. PDGFs are growth factors derived from platelets, endothelial and cancer cells. They can promote proliferation and angiogenesis through the PDGF signaling pathway in a variety of cancer types including breast (Pinto et al, 2014), bone (McGary et al, 2002), prostate (Sintich et al, 1999), and colorectal cancers (Yuge et al, 2015). Western blot analysis revealed that the phosphorylation level of ERK1/2, a key component in PDGF downstream signaling pathway, was down-regulated by the aptamer, indicating the underlying mechanism of inhibition of CRC cell proliferation. Conclusions: This study demonstrated that using a DNA aptamer to interfere with the binding of PDGF-BB to its receptor suppressed CRC cell proliferation in part via down-regulation of the Ras/Raf/MEK/ERK signaling pathway. It raised the possibility that the PDGF-BB-specific aptamer could be a promising therapeutic agent for CRC targeted therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
