Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Rm 5570, MSRB 2, 1150 West Medical Center Dr, Ann Arbor MI 48109, USA.
Anticancer Res. 2010 Dec;30(12):4805-9.
This study tested the hypothesis that response of adrenal cortical carcinoma (ACC) to pro-apoptosis drugs depends on expression of anti-apoptosis genes.
Expression of Bcl-2 and Bcl-XL proteins was determined in two human adrenal cancer cell lines, NCI-H-295 and RL-251. Two pro-apoptosis drugs, gossypol (G) and docetaxel (D) were tested in vitro and in vivo in a human ACC/SCID mouse chimera.
Bcl-XL was strongly expressed in RL-251 but not in H-295 and neither expressed the Bcl-2 protein. G and D induced greater dose-dependent inhibition of cell proliferation in RL-251 than in H-295 cells and completely suppressed growth of tumors with high expression of Bcl-XL (p<0.05) while there was no growth suppression in tumors without Bcl-XL expression.
This study provided proof of concept that expression of Bcl-XL determines response to pro-apoptosis drugs. Profiling adrenal tumors for expression of anti-apoptosis genes may provide clues to their potential response to drugs that induce apoptosis.
本研究旨在验证这样一个假设，即肾上腺皮质癌 (ACC) 对促凋亡药物的反应取决于抗凋亡基因的表达。
检测了两种人肾上腺癌细胞系 NCI-H-295 和 RL-251 中 Bcl-2 和 Bcl-XL 蛋白的表达。在人 ACC/SCID 小鼠嵌合体中，对两种促凋亡药物——棉酚 (G) 和多西紫杉醇 (D) 进行了体内和体外检测。
RL-251 中强烈表达 Bcl-XL，但在 H-295 中不表达，也不表达 Bcl-2 蛋白。G 和 D 诱导 RL-251 细胞增殖的剂量依赖性抑制作用大于 H-295 细胞，并且完全抑制了高表达 Bcl-XL 的肿瘤的生长（p<0.05），而在没有 Bcl-XL 表达的肿瘤中没有生长抑制作用。
本研究提供了概念验证，即 Bcl-XL 的表达决定了对促凋亡药物的反应。对肾上腺肿瘤进行抗凋亡基因表达谱分析可能为其对诱导细胞凋亡的药物的潜在反应提供线索。
