Original scientific paper

Inhibition of Lysophosphatidic Acid Receptor-2 Expression by RNA Interference Decreases Lysophosphatidic Acid-induced Urokinase Plasminogen Activator Activation, Cell Invasion, and Migration in Ovarian Cancer SKOV-3 Cells

Gui-li Wang ; Department of Obstetrics and Gynecology, Shandong Provincial Hospital, People's Republic of China
Ze-qing Wen ; Department of Obstetrics and Gynecology, Shandong Provincial Hospital, People's Republic of China
Wan-peng Xu ; Department of Surgery, Hospital of Weifang Medical University, Weifang, China
Zhi-yu Wang ; Ministry of Health, Jinan, China
Xue-lian Du ; Department of Obstetrics and Gynecology, Shandong Provincial Hospital, People's Republic of China
Fei Wang ; Department of Obstetrics and Gynecology, Shandong Provincial Hospital, People's Republic of China

Abstract

Aim To explore the role of lysophosphatidic acid receptor-2
(LPA2) in regulating lysophosphatidic acid (LPA)-induced urokinase
plasminogen activator (uPA) activation, cell invasion, and
migration in human ovarian cancer cell line SKOV-3.
Methods SKOV-3 cells were stimulated with LPA. Cell supernatant
uPA level and activity were measured using enzyme-linked
immunosorbent assay. LPA2 mRNA expression was inhibited
with LPA2-specific small interfering RNA (siRNA) and examined
using semiquantitative reverse transcriptase-polymerase chain reaction.
LPA-induced cell invasion and migration in transfected
cells were evaluated by a Matrigel invasion chamber and a Transwell
chemotaxis chamber, respectively.
Results LPA stimulation significantly enhanced in vitro uPA activity
in time- and dose-dependent manner. The levels of LPA-induced
uPA protein decreased by 55% in LPA2 siRNA-transfected
cells compared with negatively transfected cells at 24 hours after
being treated with 80 μmol/L LPA (0.75 ± 0.03 vs 0.34 ± 0.04,
P = 0.004). In the LPA2 specific siRNA-transfected SKOV-3 cells,
LPA treatment at 80 μmol/L induced considerably less invasion
and migration compared with negative control siRNA-transfected
SKOV-3 cells (invasion: 178 ± 17.2 vs 36.2 ± 3.3, P = 0.009;
migration: 220.4 ± 25.5 vs 57 ± 7.6, P = 0.009).
Conclusion LPA2 has an essential role in LPA-induced uPA activation
and tumor cell invasion in ovarian cancer SKOV-3 cells.

Keywords

RNA; Small Interfering/CD44/Ovarian Neoplasms/in vitro/Animal Experimentation

Hrčak ID:

26101

URI

https://hrcak.srce.hr/26101

Publication date:

15.4.2008.

Article data in other languages: croatian

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