Division of Hematology, Adnan Menderes University Medical Faculty, Aydin, Turkey.
Med Oncol. 2013;30(3):603. doi: 10.1007/s12032-013-0603-y. Epub 2013 May 19.
There are a number of studies about the effects of statins and thiazolidinediones on lymphocytes. However, there is no study about possible effects of atorvastatin and rosiglitazone on lymphocytes in patients with chronic lymphocytic leukemia (CLL). We aimed to investigate the effects of atorvastatin and rosiglitazone on CD38, ZAP-70, Annexin V and bcl-2 in lymphocytes of CLL in vitro. Seven (4 males and 3 females) patients with CLL with average age of 56 ± 8 years were enrolled to the study. The mean values of laboratory tests were as follows: hemoglobin: 12 ± 1.8 g/dl; hematocrit: %35 ± 6; platelet count: 156,000 ± 68,000/mm(3); leukocyte count: 50,500 ± 38,700/mm(3); and lymphocyte count: 45,700 ± 38,100/mm(3). The study was performed in three cell cultures groups. Mononuclear cells of blood samples from peripheral veins were separated by Ficoll method. On culture plate with 24 wells, it was suspended with 2 ml RPMI 1640. Then, the plates were incubated in %5 CO2 at 37 °C for 24 h. 5 μM atorvastatin-calcium was given to first group, 2 μM rosiglitazone maleate was given to second group, and the third group was included in the study as control group. After 24 h, the expressions of CD5, CD38, ZAP-70 and Annexin V by using flow cytometry with EPICS XL-MCL and the levels of bcl-2 by using ELISA method were re-evaluated. Two-paired Student's t test was used for comparison of the results, and p < 0.05 was accepted as a significance level. While atorvastatin and rosiglitazone did not affect the expression of CD38 and the level of bcl-2, these drugs significantly increased the level of Annexin V when compared with control group (p < 0.001). Both drugs significantly decreased the expressions of CD5 (p = 0.03) and ZAP-70 (p < 0.05) compared with control group. Atorvastatin and rosiglitazone increased apoptosis in lymphocytes of CLL in vitro. Moreover, these drugs decreased the expressions of CD5 and ZAP-70. These drugs must be studied in more detail in the pathogenesis and treatment for CLL.
有许多关于他汀类药物和噻唑烷二酮类药物对淋巴细胞影响的研究。然而，目前还没有关于阿托伐他汀和罗格列酮对慢性淋巴细胞白血病（CLL）患者淋巴细胞影响的研究。我们旨在研究阿托伐他汀和罗格列酮对体外 CLL 淋巴细胞 CD38、ZAP-70、Annexin V 和 bcl-2 的影响。7 名（4 名男性和 3 名女性）年龄在 56 ± 8 岁的 CLL 患者被纳入本研究。实验室检测的平均值如下：血红蛋白：12 ± 1.8 g/dl；红细胞压积：%35 ± 6；血小板计数：156,000 ± 68,000/mm(3)；白细胞计数：50,500 ± 38,700/mm(3)；淋巴细胞计数：45,700 ± 38,100/mm(3)。该研究在三组细胞培养物中进行。用 Ficoll 法分离外周静脉血的单核细胞。在 24 孔培养板中，用 2 ml RPMI 1640 悬浮。然后，将平板在 37°C、%5 CO2 下孵育 24 小时。第一组给予 5 μM 阿托伐他汀钙，第二组给予 2 μM 马来酸罗格列酮，第三组作为对照组纳入研究。24 小时后，通过 EPICS XL-MCL 流式细胞术评估 CD5、CD38、ZAP-70 和 Annexin V 的表达，并通过 ELISA 法评估 bcl-2 的水平。采用双样本学生 t 检验比较结果，p < 0.05 为显著性水平。阿托伐他汀和罗格列酮均未影响 CD38 的表达和 bcl-2 的水平，但与对照组相比，这些药物显著增加了 Annexin V 的水平（p < 0.001）。与对照组相比，这两种药物均显著降低了 CD5（p = 0.03）和 ZAP-70（p < 0.05）的表达。阿托伐他汀和罗格列酮在体外增加了 CLL 淋巴细胞的凋亡。此外，这些药物降低了 CD5 和 ZAP-70 的表达。这些药物在 CLL 的发病机制和治疗中必须进行更详细的研究。
