ABSTRACT
A potential role for lysophosphatidie acid (LPA) in the regulation of malignant diseases has been widely considered. Migratory response to LPA in glioma cells was almost completely inhibited by either pertussis toxin, LPA1 receptor antagonists including Ki 16425, or an inhibitor of phosphatidylinositol 3-kinase (PI3K) wortmannin. LPA action on migration was also suppressed, though incompletely by several specific inhibitors for intracellular signaling pathways such as Racl, p38 mitogen- activatcd protein kinase (p38 MAPK) and c-Jun terminal kinase (JNK), but not extracellular signal-regulated kinase. Nearly complete inhibition of the migration response to LPA, however, required simultaneous inhibition of both the p38MAPK and JNK pathways. Inhibition of Racl suppressed JNK but not p38MAPK, and dominant-negative form of Cdc42 abrogated p38MAPK activity. These findings suggest that, in glioma cells, the PI3K/Cdc42/ p38MAPK and PI3K/Racl/JNK pathways arc equally important for LPA1 receptor- mediated migration.
ABSTRACT
A potential role for lysophosphatidie acid (LPA) in the regulation of malignant diseases has been widely considered. Migratory response to LPA in glioma cells was almost completely inhibited by either pertussis toxin, LPA1 receptor antagonists including Ki 16425, or an inhibitor of phosphatidylinositol 3-kinase (PI3K) wortmannin.LPA action on migration was also suppressed, though incompletely by several specific inhibitors for intracellular signaling pathways such as Racl, p38 mitogen- activatcd protein kinase (p38 MAPK) and c-Jun terminal kinase (JNK), but not extracellular signal-regulated kinase.Nearly complete inhibition of the migration response to LPA, however, required simultaneous inhibition of both the p38MAPK and JNK pathways. Inhibition of Racl suppressed JNK but not p38MAPK, and dominant-negative form of Cdc42 abrogated p38MAPK activity. These findings suggest that, in glioma cells, the PI3K/Cdc42/ p38MAPK and PI3K/Racl/JNK pathways arc equally important for LPA1 receptor- mediated migration.
ABSTRACT
Objective To investigate the effect of the serums containing Xuefuzhuyu capsules and Xuesetong capsules on the proliferation of vascular smooth muscle cells (VSMC) induced by 1ysophosphatidie acid (LPA). Methods Rat VSMCs were obtainded by tissue-piece inoculation and divided into seven groups:blank serum group, Xuefuzhuyu (Xuesetong) capsules-containing serum group, LPA+ Xuefuzhuyu (Xuesetong, captopril) containing serum group and LPA+blank serum group. Effects of different groups on the proliferation of VSMCs was evaluated by MTT colorimetry. Analysis of cell cycle and DNA content were performed by flow cytometry. Results The optical density (OD) and the S phase fraction (SPF) of LPA+blank serum group and Xuefuzhuyu capsules-containing serum group were more increased than the blank serum group (P 0.05, P 0.05). Conclusion Xuefuzhuyu capsules and LPA promoted the proliferation of VSMCs in vitro. Xuefuzhuyu and Xuesetong capsules can inhibit the proliferation induced by LPA, and effect of Xuesetong capsules was greater. Part of the mechanism may be associated with the inhibition of DNA synthesis and preventing the transition from G0/G1 to S phase of VSMCs.