Department of Urology, University Hospital Bonn, Bonn, Germany.
Urol Oncol. 2011 Nov-Dec;29(6):815-20. doi: 10.1016/j.urolonc.2009.10.005. Epub 2009 Nov 27.
Indirubin-3'-monoxime, which is a selective and potent inhibitor of cyclin-dependent kinases (CDKs) has shown preclinical activity in several human cancer cells. This study investigated if indirubin-3'-monoxime can induce apoptosis and tumor cell death in 3 human (A498, CAKI-1, CAKI-2) and 1 murine renal cell cancer (RENCA) cell line.
The growth inhibitory and apoptosis induction properties were evaluated by EZ4U, a cytotoxic assay and by flow cytometry of annexin-V/PI staining during treatment with doses ranging from 5.0 to 15.0 μM indirubin-3'-monoxime over 72 hours. To further establish the underlying molecular targets of indirubin-3'-monoxime, survivin, a major anti-apoptotic protein was additionally determined by intracellular flow cytometry.
Our results show that indirubin-3'-monoxime induces growth arrest and apoptosis in all renal cell cancer (RCC) cell lines. All RCC lines expressed survivin. However, a clear correlation between apoptosis induction and expression of survivin was not found.
As treatment of metastatic renal cell cancer (mRCC) remains a challenge, and the need for continuing assessment of novel agents in the treatment of this disease is mandatory. Indirubin-3'-monoxime seems to be a candidate for further evaluation.
靛玉红-3'-单肟是一种选择性和有效的细胞周期蛋白依赖性激酶（CDKs）抑制剂，在几种人类癌细胞中显示出临床前活性。本研究调查靛玉红-3'-单肟是否能诱导 3 个人（A498、CAKI-1、CAKI-2）和 1 个鼠肾癌细胞（RENCA）系中的细胞凋亡和肿瘤细胞死亡。
通过 EZ4U 细胞毒性测定法和在 5.0 至 15.0 μM 靛玉红-3'-单肟剂量范围内治疗 72 小时期间用 annexin-V/PI 染色的流式细胞术评估生长抑制和诱导凋亡的特性。为了进一步确定靛玉红-3'-单肟的潜在分子靶点，还通过细胞内流式细胞术测定了主要抗凋亡蛋白 survivin。
我们的结果表明，靛玉红-3'-单肟诱导所有肾细胞癌（RCC）细胞系的生长停滞和凋亡。所有 RCC 系均表达 survivin。然而，凋亡诱导与 survivin 表达之间没有明显的相关性。
由于转移性肾细胞癌（mRCC）的治疗仍然是一个挑战，并且需要继续评估这种疾病的新药物。靛玉红-3'-单肟似乎是进一步评估的候选药物。
