维甲酸诱导白血病细胞凋亡是由肿瘤选择性死亡配体TRAIL的旁分泌作用介导的。

Retinoic acid-induced apoptosis in leukemia cells is mediated by paracrine action of tumor-selective death ligand TRAIL.

作者信息

Altucci L, Rossin A, Raffelsberger W, Reitmair A, Chomienne C, Gronemeyer H

机构信息

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, C.U. de Strasbourg, France.

出版信息

Nat Med. 2001 Jun;7(6):680-6. doi: 10.1038/89050.

DOI:10.1038/89050

PMID:11385504

Abstract

The therapeutic and preventive activities of retinoids in cancer are due to their ability to modulate the growth, differentiation, and survival or apoptosis of cancer cells. Here we show that in NB4 acute promyelocytic leukemia cells, retinoids selective for retinoic-acid receptor-alpha induced an autoregulatory circuitry of survival programs followed by expression of the membrane-bound tumor-selective death ligand, TRAIL (tumor necrosis factor-related apoptosis-inducing ligand, also called Apo-2L). In a paracrine mode of action, TRAIL killed NB4 as well as heterologous and retinoic-acid-resistant cells. In the leukemic blasts of freshly diagnosed acute promyelocytic leukemia patients, retinoic-acid-induced expression of TRAIL most likely caused blast apoptosis. Thus, induction of TRAIL-mediated death signaling appears to contribute to the therapeutic value of retinoids.

摘要

维甲酸类药物在癌症治疗和预防方面的作用，归因于它们调节癌细胞生长、分化、存活或凋亡的能力。在此我们表明，在NB4急性早幼粒细胞白血病细胞中，对维甲酸受体α具有选择性的维甲酸类药物诱导了存活程序的自动调节回路，随后膜结合肿瘤选择性死亡配体TRAIL（肿瘤坏死因子相关凋亡诱导配体，也称为Apo-2L）得以表达。以旁分泌作用模式，TRAIL杀死了NB4细胞以及异源细胞和维甲酸耐药细胞。在新诊断的急性早幼粒细胞白血病患者的白血病原始细胞中，维甲酸诱导的TRAIL表达很可能导致了原始细胞凋亡。因此，TRAIL介导的死亡信号的诱导似乎有助于维甲酸类药物的治疗价值。