|Abstract: ||"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 17b-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. 17b-Estradiol and the
inhibitors including LY294002 (Akt activation inhibitor), U0126 (ERK1/2 inhibitor), SB203580 (p38 MAPK inhibitor),
SP600125 (JNK1/2 inhibitor), QNZ (NF B inhibitor) and ICI 182 780 were further used to explore the inhibitory
effects of 17b-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 17b-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 17b-estradiol treatment significantly inhibits PGE2-induced
motility of human LoVo colon cancer cells."