Growth-inhibitory effect of phosphatidylinositol 3-kinase inhibitor on human pancreatic cancer cells and expression of Bcl-2 family.
Pancreatic cancer is one of the most devastating malignant tumors in humans and novel modalities for treatment need to be developed. We studied the mechanism of the growth-inhibitory effect of phosphatidylinositol 3-kinase (PI 3-K) inhibitor on human pancreatic cancer cells from the point of view of expression of the Bcl-2 family proteins. Growth of AsPC-1 and COLO-357 human pancreatic cancer cells was inhibited by a phosphatidylinositol 3-kinase (PI 3-K) inhibitor, wortmannin, and this growth-inhibitory effect was more marked in medium containing 10% fetal bovine serum (FBS) than in serum-free medium. In these cells, DNA fragmentation increased with the concentration of wortmannin in a dose-dependent manner. In Panc-1 human pancreatic cancer cells, cell growth and induction of DNA fragmentation were not influenced by treatment with wortmannin at concentrations up to 25 microM. Western blot analysis showed a decrease in expression of BclXL protein in AsPC-1 and COLO-357 cells by treatment with 25 microM wortmannin and this decrease was especially prominent in AsPC-1 cells. On the other hand, the expression of BclXL protein in Panc-1 cells was not influenced by treatment with wortmannin. The expression of BclXS protein was not detected by conventional Western blotting and the expression of Bcl-2 and Bax protein was not altered by wortmannin in all three cell lines. Decrease in expression of BclXL protein could be partly involved in the growth-inhibitory effect of the PI 3-K inhibitor, wortmannin, on pancreatic cancer cells. Although the growth of Panc-1 cells was not inhibited by wortmannin, PI 3-K inhibitor could still be one of the candidates for treatment of pancreatic cancer and BclXL could be a target for gene therapy.
Katayose
Kozo
K
Second Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Seki
Tetsuya
T
Ohba
Nobuyuki
N
Funatomi
Hitoshi
H
Goto
Noboru
N
Mitamura
Keiji
K
D000730:Androstadienes / Q000494:pharmacology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D019938:Cyclin D1 / Q000096:biosynthesis; D053938:DNA Fragmentation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D000081082:Phosphoinositide-3 Kinase Inhibitors; D019938:Cyclin D1; D000077191:Wortmannin