Karolinska Institutet, Center for Biosciences, Department of Biosciences and Nutrition, SE-141 83 Huddinge, Sweden.
Cancer Lett. 2010 Dec 18;299(1):54-62. doi: 10.1016/j.canlet.2010.08.003. Epub 2010 Sep 1.
Resistance to anticancer drugs is often observed in prostate cancer therapy. Kindlin-2 was recently found overexpressed during cancer progression. In this study, we examined the functional role of Kindlin-2 in cisplatin-induced prostate cancer cell death. Kindlin-2 was highly expressed in the androgen-insensitive (PC-3 and DU-145), but not in the androgen-sensitive cell lines (e.g., LNCaP). Overexpression of Kindlin-2 in LNCaP protected the cells from cisplatin-induced death, while Kindlin-2 knock-down in PC-3 cells enhanced cisplatin sensitivity. Mechanistically, Kindlin-2 regulation of the anti-apoptotic Bcl-xL may explain the increased cell death in the absence of Kindlin-2. Taken together, Kindlin-2 appears to play a functional role in prostate cancer cell sensitivity to cisplatin. Targeting Kindlin-2 may therefore improve drug efficacy and reduce drug doses, and would likely be beneficial for the treatment of prostate cancer.
在前列腺癌治疗中经常观察到抗癌药物耐药性。Kindlin-2 最近在癌症进展过程中被发现过度表达。在这项研究中，我们研究了 Kindlin-2 在顺铂诱导的前列腺癌细胞死亡中的功能作用。Kindlin-2 在雄激素不敏感（PC-3 和 DU-145）中高度表达，但在雄激素敏感的细胞系（例如 LNCaP）中不表达。Kindlin-2 在 LNCaP 中的过表达可保护细胞免受顺铂诱导的死亡，而在 PC-3 细胞中敲低 Kindlin-2 可增强顺铂敏感性。从机制上讲，Kindlin-2 对抗凋亡 Bcl-xL 的调节可以解释在缺乏 Kindlin-2 的情况下细胞死亡的增加。综上所述，Kindlin-2 似乎在前列腺癌细胞对顺铂的敏感性中发挥功能作用。因此，靶向 Kindlin-2 可能提高药物疗效并降低药物剂量，这可能对治疗前列腺癌有益。
