Abstract：
Vimentin is a main type 3 intermediate filament protein. It seems that abnormal expression of vimentin is contributed to the appearance of the aggressive feature of cancer cells. So that it has been reported that malignancy and epithelial-mesenchymal transition in solid tumors, and poor clinical outcomes in patients with lymphocytic leukemia and acute myelocytic leukemia have been associated with the high expression of vimentin. Vimentin is a non-caspase substrate of caspase-9 although its cleavage by caspase-9 in biological processes has not been reported. In the present study, we sought to understand whether vimentin cleavage mediated by caspase-9 could reverse the malignancy in leukemic cells. Herein, to address the issue, we investigated vimentin changes in differentiation and took advantage of the inducible caspase-9 (iC9)/AP1903 system in human leukemic NB4 cells. Following the transfection and treatment of the cells using the iC9/AP1903 system, vimentin expression, cleavage, and subsequently, the cell invasion and the relevant markers such as CD44 and MMP-9 were evaluated. Our results revealed the downregulation and cleavage of vimentin which attenuates the malignant phenotype of the NB4 cells. Considering the favorable effect of this strategy in keeping down the malignant features of the leukemic cells, the effect of the iC9/AP1903 system in combination with all-trans-retinoic acid (ATRA) treatment was evaluated. The obtained data prove that iC9/AP1903 significantly makes the leukemic cells more sensitive to ATRA.
摘要：
波形蛋白是一种主要的3型中间丝蛋白。似乎波形蛋白的异常表达有助于癌细胞的侵袭性特征的出现。因此，有报道说，实体肿瘤的恶性和上皮间质转化，淋巴细胞白血病和急性粒细胞白血病患者的不良临床结局与波形蛋白的高表达有关。波形蛋白是半胱天冬酶-9的非半胱天冬酶底物,尽管其在生物过程中被半胱天冬酶-9切割尚未被报道。在本研究中,我们试图了解caspase-9介导的波形蛋白裂解是否可以逆转白血病细胞的恶性肿瘤。在这里，为了解决这个问题，我们研究了波形蛋白在分化中的变化，并利用了人白血病NB4细胞中的诱导型caspase-9（iC9）/AP1903系统。在使用iC9/AP1903系统转染和处理细胞后，波形蛋白表达，乳沟,随后,评估细胞侵袭和相关标志物如CD44和MMP-9。我们的结果表明波形蛋白的下调和裂解减弱了NB4细胞的恶性表型。考虑到这种策略在抑制白血病细胞恶性特征方面的有利作用，评估了iC9/AP1903系统联合全反式维甲酸(ATRA)治疗的效果.获得的数据证明iC9/AP1903显著使白血病细胞对ATRA更敏感。
