Effects of Female Sex Hormones on Clusterin Expression and Paclitaxel Resistance in Endometrial Cancer Cell Lines

Objective: We have analyzed the association between clusterin expression in endometrial cancer cells and their resistance to paclitaxel. We also analyzed whether the effects of female sex hormones on clusterin expression by these cell lines affect their resistance to paclitaxel. Methods: The expression of estrogen receptors α and β, progesterone receptors AB and B, and clusterin mRNA and protein was assayed in the ECC-1 and KLE endometrial cancer cell lines by RT-PCR and Western blotting, respectively. The IC(50) of paclitaxel was measured in each cell line by XTT assay. Using clusterin siRNA, we analyzed the association between clusterin expression and paclitaxel IC(50) in each cell line. We also examined the effects of hormone treatment on cellular resistance to paclitaxel. Results: Paclitaxel IC(50) was significantly higher in KLE cells, which expressed higher levels of clusterin, than in ECC-1 cells, which expressed lower levels of clusterin. Conversely, incubation with clusterin siRNA significantly decreased the viability of KLE cells (P<0.001), but did not alter the viability of ECC-1 cells. Incubation with estrogen tended to increase the level of clusterin expression in these endometrial cancer cell lines, although the level of clusterin expression did not correlate with that of estrogen receptors. Incubation with progesterone did not alter the levels of expression of clusterin and clusterin receptor. Incubation with estrogen and paclitaxel significantly increased the viability of ECC-1 (P<0.001) but not KLE cells. Conclusion: Estrogen increases the paclitaxel resistance of endometrial cancer cell lines, by increasing clusterin expression.