Paclitaxel inhibits expression of heat shock protein 27 in ovarian and uterine cancer cells.
The purpose of the study was to determine whether paclitaxel inhibits the expression of heat shock protein 27 (HSP27) in two gynecologic cancer cell lines compared with other antineoplastic agents having different cytotoxic mechanisms. BG-1 ovarian cancer cells and HeLa uterine cancer cells were treated with a tubulin depolymerization inhibitor (paclitaxel), a topoisomerase-II inhibitor (etoposide), and two tubulin polymerization inhibitors (colcemid and vincristine). Cell kills were evaluated by counting the number of cells. Propidium iodide staining and flow cytometric analysis were applied for the determination of cell-cycle perturbation. HSP27 was stained by the indirect immunofluorescence technique and analyzed with a flow cytometer. In both BG-1 and HeLa cells, growth arrest and G2 / M accumulation were dependent on the dose of each cytotoxic agent. There were positive correlations between HSP27 overexpression and growth arrest and G2 / M accumulation when the cell lines were treated with etoposide, colcemid, or vincristine, but not with paclitaxel. Paclitaxel completely inhibited the expression of HSP27. The results of this study indicated that paclitaxel may possess unique mechanisms able to overcome drug resistance by inhibiting HSP27 expression.
Tanaka
Y
Y
Department of Obstetrics and Gynecology, Kawasaki Medical School, Kurashiki-City, Japan.
Fujiwara
K
K
Tanaka
H
H
Maehata
K
K
Kohno
I
I
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003703:Demecolcine / Q000627:therapeutic use; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000627:therapeutic use*; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014750:Vincristine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D006360:Heat-Shock Proteins; D014750:Vincristine; D005047:Etoposide; D017239:Paclitaxel; D003703:Demecolcine