Institute of Cellular and System Medicine and Translational Center for Glandular Malignancies, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan, ROC.
Anticancer Res. 2010 Sep;30(9):3643-8.
Previously, we and other groups reported that liver X receptor (LXR) agonists T0901317, 22(R)-hydroxycholesterol, and 24(S)-hydroxycholesterol suppressed the proliferation of prostate and breast cancer cells. In this study, we report that T0901317 and 22(R)-hydroxycholesterol treatment inhibited the proliferation of different progression stages of LNCaP human prostate cancer cells, as well as different commonly used human cancer cell lines. Cancer cell lines with higher LXRα mRNA expression were more sensitive to 22(R)-hydroxycholesterol-induced inhibition. T0901317 treatment decreased the percentage of the cell population in S-phase and caused G(1) cell cycle arrest. Overexpression of S-phase kinase-associated protein 2 (Skp2) partially blocked the suppressive effect of T0901317 treatment. Modulating LXR signaling is therefore a potential adjuvant therapy for advanced prostate cancer and other types of cancer.
先前，我们和其他小组报道肝 X 受体（LXR）激动剂 T0901317、22(R)-羟基胆固醇和 24(S)-羟基胆固醇抑制前列腺癌和乳腺癌细胞的增殖。在这项研究中，我们报告 T0901317 和 22(R)-羟基胆固醇处理抑制了不同进展阶段的 LNCaP 人前列腺癌细胞以及不同常用的人癌细胞系的增殖。LXRα mRNA 表达水平较高的癌细胞系对 22(R)-羟基胆固醇诱导的抑制更为敏感。T0901317 处理降低了 S 期细胞群体的百分比，并导致 G1 细胞周期停滞。S 期激酶相关蛋白 2（Skp2）的过表达部分阻断了 T0901317 处理的抑制作用。因此，调节 LXR 信号传导是晚期前列腺癌和其他类型癌症的一种潜在辅助治疗方法。
