Polioudaki H, Kastrinaki M-C, Papadaki H A, Theodoropoulos P A
Department of Biochemistry, School of Medicine, University of Crete, Crete, Greece.
Cell Prolif. 2009 Aug;42(4):434-47. doi: 10.1111/j.1365-2184.2009.00607.x. Epub 2009 May 22.
This study aimed to investigate molecular and cellular changes induced in human bone marrow mesenchymal stem cells (hMSCs) after treatment with microtubule-interacting agents and to estimate damage to the bone marrow microenvironment caused by chemotherapy.
Using an in vitro hMSC culture system and biochemical and morphological approaches, we studied the effect of nocodazole and taxol(R) on microtubule and nuclear envelope organization, tubulin and p53 synthesis, cell cycle progression and proliferation and death of hMSCs isolated from healthy donors.
Both nocodazole and taxol reduced hMSC proliferation and induced changes in the microtubular network and nuclear envelope morphology and organization. However, they exhibited only a moderate effect on cell death and partial arrest of hMSCs at G(2) but not at M phase of the cell cycle. Both agents induced expression of p53, exclusively localized in abnormally shaped nuclei, while taxol, but not nocodazole, increased synthesis of beta-tubulin isoforms. Cell growth rates and microtubule and nuclear envelope organization gradually normalized after transfer, in drug-free medium. Our data indicate that microtubule-interacting drugs reversibly inhibit proliferation of hMSCs; additionally, their cytotoxic action and effect on microtubule and nuclear envelope organization are moderate and reversible. We conclude that alterations in human bone marrow cells of patients under taxol chemotherapy are transient and reversible.
本研究旨在调查用微管相互作用剂处理后人骨髓间充质干细胞（hMSCs）中诱导的分子和细胞变化，并评估化疗对骨髓微环境造成的损伤。
使用体外hMSC培养系统以及生化和形态学方法，我们研究了诺考达唑和紫杉醇对从健康供体分离的hMSCs的微管和核膜组织、微管蛋白和p53合成、细胞周期进程以及增殖和死亡的影响。
诺考达唑和紫杉醇均降低了hMSC的增殖，并诱导了微管网络以及核膜形态和组织的变化。然而，它们对细胞死亡仅表现出中等程度的影响，并且使hMSCs在细胞周期的G2期而非M期部分停滞。两种药物均诱导了p53的表达，p53仅定位在异常形状的细胞核中，而紫杉醇而非诺考达唑增加了β-微管蛋白亚型的合成。在无药物培养基中传代后，细胞生长速率以及微管和核膜组织逐渐恢复正常。我们的数据表明，微管相互作用药物可逆地抑制hMSCs的增殖；此外，它们的细胞毒性作用以及对微管和核膜组织的影响是中等程度且可逆的。我们得出结论，接受紫杉醇化疗的患者的人骨髓细胞变化是短暂且可逆的。
