- 作者: Hsi-Hsien Hsu, Wei-Syun Hu, Yueh-Min Lin, Wei-Wen Kuo, Li-Mien Chen, Wei-Kung Chen, Jin-Ming Hwang, Fuu-Jen Tsai, Chung-Jung Liu and Chih-Yang Huang
- 作者服務機構: Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Background: Epidemiological studies demonstrate that the incidence and
mortality rates of colorectal cancer in women are lower than in men. However, it is
unknown if 17β-estradiol treatment is sufficient to inhibit prostaglandin E2
(PGE2)-induced cellular motility in human colon cancer cells.
Methods: We analyzed the protein expression of urokinase plasminogen
activator (uPA), tissue plasminogen activator (tPA), matrix metallopeptidases
(MMPs), plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitor of
metalloproteinases (TIMPs), and the cellular motility in PGE2-stimulated human
LoVo cells. 17β-Estradiol and the inhibitors including LY294002 (Akt activation
inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor), SP600125
(JNK1/2 inhibitor), QNZ (NFκB inhibitor) and ICI 182 780 were further used to
explore the inhibitory effects of 17β-estradiol on PGE2-induced LoVo cell motility.
Student’s t-test was used to analyze the difference between the two groups.
Results: Upregulation of urokinase plasminogen activator (uPA), tissue
plasminogen activator (tPA) and matrix metallopeptidases (MMPs) is reported to
associate with the development of cancer cell mobility, metastasis, and subsequent
malignant tumor. After administration of inhibitors including LY294002, U0126,
SB203580, SP600125 or QNZ, we found that PGE2 treatment up-regulated uPA and
MMP-9 expression via JNK1/2 signaling pathway, thus promoting cellular motility in
human LoVo cancer cells. However, PGE2 treatment showed no effects on regulating
expression of tPA, MMP-2, plasminogen activator inhibitor-1 (PAI-1), tissue inhibitor
of metalloproteinase-1, -2, -3 and -4 (TIMP-1, -2, -3 and -4). We further observed that
17β-estradiol treatment inhibited PGE2-induced uPA, MMP-9 and cellular motility by
suppressing activation of JNK1/2 in human LoVo cancer cells.
Conclusions: Collectively, these results suggest that 17β-estradiol treatment
significantly inhibits PGE2-induced motility of human LoVo colon cancer cells.
- 中文關鍵字: --
- 英文關鍵字: --