Chen Z M, Wu Q, Chen Y Q, Su W J
State Lab. for Tumor Cell Engineering, Xiamen Univ., Xiamen 361005.
Shi Yan Sheng Wu Xue Bao. 1999 Jun;32(2):135-40.
Retinoic acid can induce growth inhibition and apoptosis, and regulate cell cycle in many types of cancer cell lines. In this study, we investigated the role of all-trans retinoic acid (ATRA) and its mechanism of action in human gastric cancer cell lines. Our results demonstrated that ATRA effectively inhibited growth in three of four gastric cancer cell lines by induction of G0/G1 arrest, and did not induce apoptosis in four gastric cancer cell lines. In RA-sensitive cell lines, ATRA-induced G0/G1 arrest is associated with down regulaton of c-myc and hyperphosphorylated Rb expression, and up regulation of p21WAF1/CIP1 and p53 expression. There were no significant changes in cyclin D1 or CDK4 expression induced by ATRA. Futhermore, expression of these genes were not regulated by ATRA in ATRA-resistant gastric cancer cell line. These results indicate that growth inhibition, rather than apoptosis, is correlated with G0/G1 arrest of these cell lines, more important molecules related cell cycle, including c-myc, p21WAF1/CIP1, p53 and Rb, are involveed in regulation of cell cycle in gastric cancer cells.
维甲酸可诱导多种癌细胞系的生长抑制和凋亡,并调节细胞周期。在本研究中,我们调查了全反式维甲酸(ATRA)在人胃癌细胞系中的作用及其作用机制。我们的结果表明,ATRA通过诱导G0/G1期阻滞有效抑制了四种胃癌细胞系中三种的生长,且未在四种胃癌细胞系中诱导凋亡。在对维甲酸敏感的细胞系中,ATRA诱导的G0/G1期阻滞与c-myc的下调和Rb的过度磷酸化表达相关,以及p21WAF1/CIP1和p53表达的上调有关。ATRA诱导的细胞周期蛋白D1或细胞周期蛋白依赖性激酶4表达无显著变化。此外,在对ATRA耐药的胃癌细胞系中,这些基因的表达不受ATRA调节。这些结果表明,生长抑制而非凋亡与这些细胞系的G0/G1期阻滞相关,包括c-myc、p21WAF1/CIP1、p53和Rb等与细胞周期更相关的重要分子参与了胃癌细胞周期的调节。