Sumantran V N, Ealovega M W, Nuñez G, Clarke M F, Wicha M S
Department of Internal Medicine, University of Michigan Comprehensive Cancer Center, Ann Arbor 48109-0724, USA.
Cancer Res. 1995 Jun 15;55(12):2507-10.
Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy. We report that Bcl-XL, which functions like Bcl-2 to inhibit apoptosis, is highly expressed in MCF-7 human breast carcinoma cells. We used Bcl-XS, a dominant negative inhibitor of Bcl-2 and Bcl-XL, to demonstrate the role of these genes in modulating chemotherapy-induced apoptosis. Bcl-XS overexpressed in MCF-7 cells by stable transfection does not affect viability by itself but induces a marked increase in chemosensitivity to VP-16 or taxol. Using an ELISA assay which quantitates DNA damage, we demonstrate that this sensitization is due to apoptosis, suggesting the therapeutic utility of targeting this pathway.
对凋亡的抗性在对化疗难治的肿瘤中起重要作用。我们报告称，功能与Bcl-2相似、可抑制凋亡的Bcl-XL在MCF-7人乳腺癌细胞中高表达。我们使用Bcl-XS（一种Bcl-2和Bcl-XL的显性负性抑制剂）来证明这些基因在调节化疗诱导的凋亡中的作用。通过稳定转染在MCF-7细胞中过表达的Bcl-XS本身不影响细胞活力，但可显著增加对VP-16或紫杉醇的化学敏感性。使用定量DNA损伤的ELISA检测方法，我们证明这种致敏作用是由于凋亡，这表明靶向该途径具有治疗效用。
