Dual modes of death induced by etoposide in human epithelial tumor cells allow Bcl-2 to inhibit apoptosis without affecting clonogenic survival.
Dual modes of death induced by etoposide in human epithelial tumor cells allow Bcl-2 to inhibit apoptosis without affecting clonogenic survival.
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发表时间：
1996-09
期刊：
影响因子：
11.2
通讯作者：
Richard B. Lock;L. Stribinskiene
中科院分区：
文献类型：
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作者：
Richard B. Lock;L. Stribinskiene
Bcl-2癌蛋白在多种人类恶性肿瘤中表达，可阻断化疗药物（包括拓扑异构酶II抑制剂依托泊苷）诱导的细胞凋亡。为探讨Bcl-2在足叶乙甙诱导的人上皮性肿瘤细胞死亡中的意义，将人bcl-2 cDNA与pSFFV表达载体共转染HeLa S3细胞，建立稳定表达Bcl-2的克隆。与以前的研究一致，Bcl-2抑制细胞活力的丧失（通过台盼蓝排除法），形态学凋亡细胞的出现，以及依托泊苷暴露后（25微米，4小时）提取的低分子量DNA的量。与野生型和载体对照转染的克隆相比，抑制的程度根据研究的两个克隆中Bcl-2蛋白表达的水平而不同。然而，当通过集落形成试验评估细胞存活率时，在使用的任何依托泊苷浓度下均未检测到显著差异。虽然Bcl-2抑制足叶乙甙诱导的细胞凋亡，但它对有丝分裂灾难特征的巨大多核细胞的形成没有影响。因此，Bcl-2防止化疗药物引起的细胞凋亡的能力可能不一定转化为表达Bcl-2的细胞的存活率增加。
The Bcl-2 oncoprotein, which is expressed in a variety of human malignancies, blocks apoptosis induced by chemotherapeutic drugs, including the topoisomerase II inhibitor, etoposide. To determine the significance of Bcl-2 in etoposide-induced death of human epithelial tumor cells, HeLa S3 cells were transfected with human bcl-2 cDNA in the pSFFV expression vector, and stable Bcl-2-expressing clones established. In agreement with previous studies, Bcl-2 inhibited loss of cell viability (by trypan blue exclusion), the appearance of morphologically apoptotic cells, and the amount of low molecular weight DNA extracted after etoposide exposure (25 microns, 4 h). The degree of inhibition, compared to wild-type and vector control-transfected clones, differed according to the level of Bcl-2 protein expressed in the two clones studied. However, when cell survival was assessed by colony-forming assays, no significant differences were detected at any of the etoposide concentrations used. Although Bcl-2 inhibited etoposide-induced apoptosis, it had no effect on the formation of giant, multinucleated cells characteristic of mitotic catastrophe. Consequently, the ability of Bcl-2 to prevent apoptosis caused by chemotherapeutic drugs may not necessarily translate into increased survival of cells that express Bcl-2.