TY - JOUR
T1 - Prostaglandin E2-induced COX-2 expressions via EP2 and EP4 signaling pathways in human LoVo colon cancer cells
AU - Hsu, Hsi Hsien
AU - Lin, Yueh Min
AU - Shen, Chia Yao
AU - Shibu, Marthandam Asokan
AU - Li, Shin Yi
AU - Chang, Sheng Huang
AU - Lin, Chien Chung
AU - Chen, Ray Jade
AU - Viswanadha, Vijaya Padma
AU - Shih, Hui Nung
AU - Huang, Chih Yang
N1 - Funding Information:
This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW106-TDU-B-212-113004).
Publisher Copyright:
© 2017 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Metastasis is the most dangerous risk faced by patients with hereditary non-polyposis colon cancer (HNPCC). The expression of matrix metalloproteinases (MMPs) has been observed in several types of human cancers and regulates the efficacy of many therapies. Here, we show that treatment with various concentrations of prostaglandin E2 (PGE2; 0, 1, 5 or 10 αM) promotes the migration ability of the human LoVo colon cancer cell line. As demonstrated by mRNA and protein expression analyses, EP2 and EP4 are the major PGE2 receptors expressed on the LoVo cell membrane. The Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt cell survival pathway was upregulated by EP2 and EP4 activation. Following the activation of the PI3K/Akt pathway, β-catenin translocated into the nucleus and triggered COX2 transcription via LEF-1 and TCF-4 and its subsequent translation. COX2 expression correlated with the elevation in the migration ability of LoVo cells. The experimental evidence shows a possible mechanism by which PGE2 induces cancer cell migration and further suggests PGE2 to be a potential therapeutic target in colon cancer metastasis. On inhibition of PGE2, in order to determine the downstream pathway, the levels of PI3K/Akt pathway were suppressed and the β-catenin expression was also modulated. Inhibition of EP2 and EP4 shows that PGE2 induces protein expression of COX-2 through EP2 and EP4 receptors in LoVo colon cancer cells.
AB - Metastasis is the most dangerous risk faced by patients with hereditary non-polyposis colon cancer (HNPCC). The expression of matrix metalloproteinases (MMPs) has been observed in several types of human cancers and regulates the efficacy of many therapies. Here, we show that treatment with various concentrations of prostaglandin E2 (PGE2; 0, 1, 5 or 10 αM) promotes the migration ability of the human LoVo colon cancer cell line. As demonstrated by mRNA and protein expression analyses, EP2 and EP4 are the major PGE2 receptors expressed on the LoVo cell membrane. The Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt cell survival pathway was upregulated by EP2 and EP4 activation. Following the activation of the PI3K/Akt pathway, β-catenin translocated into the nucleus and triggered COX2 transcription via LEF-1 and TCF-4 and its subsequent translation. COX2 expression correlated with the elevation in the migration ability of LoVo cells. The experimental evidence shows a possible mechanism by which PGE2 induces cancer cell migration and further suggests PGE2 to be a potential therapeutic target in colon cancer metastasis. On inhibition of PGE2, in order to determine the downstream pathway, the levels of PI3K/Akt pathway were suppressed and the β-catenin expression was also modulated. Inhibition of EP2 and EP4 shows that PGE2 induces protein expression of COX-2 through EP2 and EP4 receptors in LoVo colon cancer cells.
KW - COX-2
KW - EP2 and EP4 receptors
KW - Hereditary non-polyposis colon cancer (HNPCC)
KW - Prostaglandin E2 (PGE2)
KW - β-catenin
UR - http://www.scopus.com/inward/record.url?scp=85019754319&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019754319&partnerID=8YFLogxK
U2 - 10.3390/ijms18061132
DO - 10.3390/ijms18061132
M3 - Article
C2 - 28587064
AN - SCOPUS:85019754319
SN - 1661-6596
VL - 18
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 6
M1 - A1132
ER -
