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Folate receptor alpha (FRα) is overexpressed in > 80% of epithelial ovarian cancer (EOC). Accordingly, folate is attracting attention as a targeting ligand for EOC. For EOC patients, paclitaxel (PTX) is generally used as first-line chemotherapeutic agent in combination with platinum-based drugs. Cyclodextrin (CyD) is a potential new formulation vehicle for PTX that could replace Cremophor-EL, a traditional formulation vehicle that causes significant side effects including neutropenia. Recently, folate-appended β-CyD (Fol-c -β-CyD) was developed as an FRα-targeting drug carrier, but its efficacy as a treatment for EOC remains to be determined. In this study, we assessed the antitumor activity of PTX in Fol-c -β-CyD (PTX/Fol-c -β-CyD) in EOC-derived cell lines. We found that PTX/Fol-c -β-CyD killed not only FRα-expressing cells, but also FRα-negative cells. In the FRα-negative A2780 cells, knockdown of proton-coupled folate transporter (PCFT) significantly decreased the cytotoxicity of PTX/Fol-c -β-CyD, whereas knockdown of FRα did not. By contrast, knockdown of either FRα or PCFT decreased the cytotoxicity of PTX/Fol-c -β-CyD in FRα-expressing SK-OV-3 cells. Furthermore, the cytotoxicity of PTX/Fol-c -β-CyD in A2780 cells was increased at acidic pH, and this increase was suppressed by PCFT inhibitor. In mice intraperitoneally inoculated with FRα-expressing or PCFT-expressing EOC cells, intraperitoneal administration of PTX/Fol-c -β-CyD significantly suppressed the growth of both types of EOC cells relative to PTX alone, without inducing a significant change in the neutrophil/white blood cell ratio. Our data suggest that Fol-c -β-CyD targets not only FRα but also PCFT, and can efficiently deliver anticancer drugs to EOC cells in the peritoneal cavity.
This article was published in the following journal.
Name: Cancer science
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A subtype of GPI-anchored folate receptors that is expressed in tissues of epithelial origin. This protein is also identified as an ovarian-tumor-specific antigen.
A subtype of GPI-anchored folate receptors that is expressed in PLACENTA and hematopoietic cells.
Derivative of beta-cyclodextrin that is used as an excipient for steroid drugs and as a lipid chelator.
Autosomal dominant HEREDITARY CANCER SYNDROME in which a mutation most often in either BRCA1 or BRCA2 is associated with a significantly increased risk for breast and ovarian cancers.
Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.
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Women's Health - key topics include breast cancer, pregnancy, menopause, stroke Follow and track Women's Health News on BioPortfolio: Women's Health News RSS Women'...