Y. Do Yoo et al., CDK4 down-regulation induced by paclitaxel is associated with G(1) arrest in gastric cancer cells, CLIN CANC R, 4(12), 1998, pp. 3063-3068
Paclitaxel induces a cell cycle block at G(2)-M phase by preventing the dep
olymerization of microtubules and induces p53-independent apoptosis in many
cancer cells, We observed that gastric cancer cells treated with paclitaxe
l have shown a cyclin-dependent kinase (CDK)4 do down-regulation, This pacl
itaxel-induced CDK4 down-regulation resulted in a cell cycle arrest at G(1)
-S phase. To confirm this observation,,ve prepared stable transfectants tha
t overexpressed CDK4 and analyzed the cell cycle progression. Ectopic expre
ssion of CDK4 in SNU cells resulted in a release of paclitaxel-induced G(1)
arrest. The release of G(1) arrest by enforced expression of CDK4 seems to
make the cells more sensitive to paclitaxel-induced apoptosis. From this f
inding, we could then suggest that paclitaxel treatment induces both G(1)-S
and G(2)-M blocks in the cell cycle progression of gastric cancer cells.