17beta-estradiol inhibits prostaglandin E2-induced COX-2 expressions and cell migration by suppressing Akt and ERK1/2 signaling pathways in human LoVo colon cancer cells.
Epidemiological studies demonstrate that the incidence and mortality rates of colorectal cancer in women are lower than in men. However, it is unknown if 17beta-estradiol treatment is sufficient to inhibit prostaglandin E2 (PGE2)-induced cellular motility in human colon cancer cells. Upregulation of cyclooxygenase-2 (COX-2) is reported to associate with the development of cancer cell mobility, metastasis, and subsequent malignant tumor. After administration of inhibitors including LY294002 (Akt activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125 (JNK1/2 inhibitor), or QNZ (NFkappaB inhibitor), we found that PGE2 treatment increases COX-2 via Akt and ERK1/2 pathways, thus promoting cellular motility in human LoVo cancer cells. We further observed that 17beta-estradiol treatment inhibits PGE2-induced COX-2 expression and cellular motility via suppressing activation of Akt and ERK1/2 in human LoVo cancer cells. Collectively, these results suggest that 17beta-estradiol treatment dramatically inhibits PGE2-induced progression of human LoVo colon cancer cells.
Lai
Tung-Yuan
TY
College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan.
Chen
Li-Mien
LM
Lin
Jing-Ying
JY
Tzang
Bor-Show
BS
Lin
James A
JA
Tsai
Chang-Hai
CH
Lin
Yueh-Min
YM
Huang
Chih-Yang
CY
Liu
Chung-Jung
CJ
Hsu
Hsi-Hsien
HH
D002465:Cell Movement / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004958:Estradiol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D015232:Dinoprostone
J Natl Cancer Inst. 1995 Apr 5;87(7):517-23
7707438
N Engl J Med. 2004 Mar 4;350(10):991-1004
14999111
Annu Rev Biochem. 2000;69:145-82
10966456
J Natl Cancer Inst. 2002 Feb 20;94(4):252-66
11854387
CA Cancer J Clin. 2002 Jan-Feb;52(1):23-47
11814064
CA Cancer J Clin. 2005 Jan-Feb;55(1):10-30
15661684
Cancer Res. 2002 May 1;62(9):2522-30
11980644
N Engl J Med. 2000 Jun 29;342(26):1946-52
10874062
Am J Med. 1998 Mar 30;104(3A):2S-8S; discussion 21S-22S
9572314
FEBS Lett. 2008 Oct 15;582(23-24):3415-22
18789327
Ann Intern Med. 1998 May 1;128(9):705-12
9556463
Cancer Res. 2007 May 1;67(9):4320-7
17483345
J Pharmacol Exp Ther. 2008 Dec;327(3):863-71
18784349
Srp Arh Celok Lek. 2008 Mar-Apr;136(3-4):187-92
18720757
Cancer Sci. 2008 Nov;99(11):2120-7
18823380
Chem Biol. 1996 Jul;3(7):529-36
8807884
Gastroenterology. 1994 Oct;107(4):1183-8
7926468
Neoplasia. 2000 Nov-Dec;2(6):523-30
11228545
CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29
14974761
Curr Genomics. 2006;7(8):497-508
18369406
J Biol Chem. 1998 Jan 23;273(4):2424-8
9442092
Mol Cancer Ther. 2004 Aug;3(8):1031-9
15299086
Cancer. 1992 Sep 1;70(5 Suppl):1206-15
1511368
Cell. 1996 Nov 29;87(5):803-9
8945508
Cancer Res. 2001 Feb 15;61(4):1733-40
11245490
Best Pract Res Clin Endocrinol Metab. 2003 Mar;17(1):139-47
12763517
Cancer Res. 2001 Jan 15;61(2):632-40
11212261
J Biol Chem. 2000 May 19;275(20):14838-45
10809726
J Nutr Biochem. 2009 Sep;20(9):663-76
18824345
J Clin Invest. 1997 May 1;99(9):2254-9
9151799
J Clin Gastroenterol. 2007 Sep;41(8):731-46
17700421
Int Immunopharmacol. 2008 Dec 20;8(13-14):1821-6
18801463
Trends Pharmacol Sci. 2003 Feb;24(2):96-102
12559775