Paclitaxel inhibits ovarian tumor growth by inducing epithelial cancer cells to benign fibroblast-like cells.
Paclitaxel is commonly used to treat multiple human malignancies, but its mechanism of action is still poorly defined. Human ovarian cancer SKOV3 cells (parental SKOV3) were treated with paclitaxel (1μM) for 2days, and the morphologic changes in the cells were monitored for more than 4months. Parental SKOV3 underwent a markedly morphologic transition from the epithelial to fibroblast-like phenotype following treatment with paclitaxel; the resulting cells were designated as SKOV3-P. The SKOV3-P cells' proliferative ability was assessed via a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The molecular characteristics of these cells were assessed via immunocytochemical staining and Western blot analysis. Their invasiveness and tumor formation ability was evaluated via wound-scratch and colony formation assays. The tumorigenicity of SKOV3-P cells was assessed in vivo after subcutaneous injection of tumor cells between injections of parental and paclitaxel-treated cells in nude mice. SKOV3-P cells have decreased the proliferation and invasion ability, decreased colony-forming ability when cultured in Matrigel and lost their tumor formation as compared with parental SKOV3 cells when injected in nude mice. SKOV3-P cells have decreased expression of E-cadherin, cytokeratin, Snail, PI3K, and P-Akt-Ser473, and increased expression of fibronectin, vimentin, Slug, P27, and PTEN. These results demonstrated that paclitaxel can inhibit tumor growth by inducing ovarian cancer epithelial cells toward a benign fibroblast-like phenotype through dysregulation of previously known pathways involved in the regulation of epithelial to mesenchymal transition (EMT), which may represent a novel mechanism for paclitaxel-induced tumor suppression.
Department of Pathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
Lizhou
L
Jia
Shiwu
S
Zhang
Yanfen
Y
Ye
Xin
X
Li
Imelda
I
Mercado-Uribe
Robert C
RC
Bast
Jinsong
J
Liu
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D009375:Neoplasms, Glandular and Epithelial / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel