Department of Anesthesiology, University Medical Center Regensburg, Franz Josef Strauss Allee 11, 93053, Regensburg, Germany.
Eur J Med Res. 2019 Jan 28;24(1):5. doi: 10.1186/s40001-019-0365-x.
Cancer, one of the leading causes of death worldwide, develops when the normal balance between mitosis and apoptosis is disrupted. The subsequently increased proliferation rate or decreased apoptosis rate of cells leads to uncontrolled cellular growth. Thus, the current aim of cancer research is to increase the apoptosis rate in tumor cells-while limiting the concurrent death of healthy cells-and to induce controlled apoptosis in abnormal cells. Staurosporine is a very potent inducer of apoptosis because it inhibits many different kinases. So far, many different kinase pathways of staurosporine-induced apoptosis have been discussed for various tumor entities.
To identify the effect of staurosporine in pancreatic and colorectal carcinoma cells and its apoptosis-inducing signaling pathway.
The apoptosis rate in pancreatic and colorectal carcinoma cells was analyzed by annexin V staining after staurosporine administration. Staurosporine stimulation and its effects on the expression of Bcl2, BAX, Bad, caspase-8, and caspase-9 were investigated with immunoblot.
Staurosporine significantly increased apoptosis in pancreatic carcinoma cells. Western blot analysis showed activation of caspase-9 in PaTu 8988t and Panc-1 cells with 1 µM staurosporine. In addition, expression of Bcl2 and Bad was decreased in PaTu 8988t cells. In colorectal carcinoma cells SW 480, staurosporine stimulation did not induce apoptosis.
Modern therapeutic strategies for tumor diseases target the efficient modulation of specific signaling and transcription pathways. In this respect, the therapeutic potential of protein kinase inhibitors has been repeatedly discussed. Our study showed that staurosporine induces apoptosis in pancreatic carcinoma cells via the intrinsic signaling pathway. Thus, staurosporine is a suitable positive control for in vitro apoptosis tests for the pancreatic cancer cell lines PaTu 8988t and Panc-1. Further clinical studies should analyze the impact of this finding on cancer treatment.
癌症是全球主要死因之一，当有丝分裂和细胞凋亡之间的正常平衡被打破时，癌症就会发生。细胞的增殖率增加或凋亡率降低，导致细胞不受控制地生长。因此，癌症研究的当前目标是增加肿瘤细胞中的凋亡率——同时限制健康细胞的同步死亡——并诱导异常细胞的可控凋亡。星形孢菌素是一种非常有效的凋亡诱导剂，因为它可以抑制许多不同的激酶。到目前为止，已经针对各种肿瘤实体讨论了星形孢菌素诱导凋亡的许多不同的激酶途径。
确定星形孢菌素对胰腺和结直肠癌细胞的作用及其诱导凋亡的信号通路。
用星形孢菌素处理后，通过 Annexin V 染色分析胰腺和结直肠癌细胞的凋亡率。用免疫印迹法研究星形孢菌素刺激及其对 Bcl2、BAX、Bad、caspase-8 和 caspase-9 表达的影响。
星形孢菌素显著增加胰腺癌细胞的凋亡。Western blot 分析显示，1µM 星形孢菌素激活了 PaTu 8988t 和 Panc-1 细胞中的 caspase-9。此外，PaTu 8988t 细胞中 Bcl2 和 Bad 的表达减少。在结直肠癌细胞 SW 480 中，星形孢菌素刺激不会诱导凋亡。
肿瘤疾病的现代治疗策略针对特定信号和转录途径的有效调节。在这方面，蛋白激酶抑制剂的治疗潜力已被反复讨论。我们的研究表明，星形孢菌素通过内在信号通路诱导胰腺癌细胞凋亡。因此，星形孢菌素是 PaTu 8988t 和 Panc-1 胰腺癌细胞系体外凋亡试验的合适阳性对照。进一步的临床研究应分析这一发现对癌症治疗的影响。
