Piontek M, Porschen R
Department of Gastroenterology, Heinrich-Heine-University, Düsseldorf, Germany.
J Cancer Res Clin Oncol. 1994;120(12):695-9. doi: 10.1007/BF01194265.
We have studied the ability of cyclosporin A (CsA) to inhibit the growth of human AGS gastric and HT29 colon carcinoma cells in vitro. Using continuous drug exposure in growth assays of cultured tumour cells we found that CsA produced a dose-dependent growth inhibition in gastric and colon cancer cells with a half-maximal effect at 5 microM and 6 microM CsA respectively. The growth inhibition of CsA was reversible in AGS cells, when the tumour cells were incubated in normal growth medium following CsA treatment. Trypan blue dye exclusion in AGS cells indicated a cytostatic rather than a cytotoxic effect in the concentration range used. Coincubation of CsA-treated cells with 10-400 U/ml interleukin-2 (IL-2) could not abrogate this growth inhibition, suggesting an IL-2 independent mechanism of action. Flow-cytometric analysis did not reveal a phase arrest of the gastric cancer cells within the cell cycle. We conclude from our experiments that CsA cytostatically and reversibly inhibits the growth of human gastric cancer cells in a dose-dependent manner. In contrast to its mechanism of action in lymphocytes, this direct antiproliferative effect of CsA seems not to be mediated by an IL-2-dependent pathway or a cell-cycle-phase arrest of the tumour cells.
我们研究了环孢素A（CsA）在体外抑制人AGS胃癌细胞和HT29结肠癌细胞生长的能力。在培养肿瘤细胞的生长试验中采用持续药物暴露，我们发现CsA对胃癌细胞和结肠癌细胞产生剂量依赖性生长抑制，分别在5微摩尔/升和6微摩尔/升CsA时达到最大效应的一半。当肿瘤细胞在CsA处理后于正常生长培养基中孵育时，CsA对AGS细胞的生长抑制是可逆的。在所用浓度范围内，AGS细胞中的台盼蓝染料排斥试验表明其具有细胞抑制而非细胞毒性作用。将经CsA处理的细胞与10 - 400单位/毫升白细胞介素-2（IL-2）共同孵育不能消除这种生长抑制，提示其作用机制不依赖于IL-2。流式细胞术分析未显示胃癌细胞在细胞周期内出现阶段停滞。我们从实验得出结论，CsA以剂量依赖性方式对人胃癌细胞产生细胞抑制且可逆的生长抑制作用。与其在淋巴细胞中的作用机制不同，CsA的这种直接抗增殖作用似乎不是由IL-2依赖性途径或肿瘤细胞的细胞周期阶段停滞介导的。
