视黄酸对胃癌细胞周期的调控

视黄酸(RA)能够抑制许多类型癌细胞生长、诱导细胞凋亡和调节细胞周期。本文研究了全反式视黄酸(ATRA)对人胃癌细胞的作用机理。结果表明,ATRA通过诱导细胞滞留在G_0/G_1期而显著抑制胃癌细胞生长,但ATRA不能诱导胃癌细胞凋亡;ATRA调控细胞周期与c-myc、磷酸化Rb水平的下调和p21~(WAF1/CIP1)、p53水平的上调有关,而cyclinD_1和CDK_4水平没有明显变化。在RA抗性细胞中,ATRA不能调节这些基因表达。结果证实,ATRA对胃癌细胞生长抑制与其诱导细胞滞留在G_0/G_1期有关,而与细胞凋亡的诱导无关,许多重要的、与周期相关的分子,包括cmyc、p21~(WAF1/CIP1、p53和Rb等参与细胞周期的调控。

REGULATION OF CELL CYCLE BY RETINOIC ACID IN GASTRIC CANCER CELLS

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 (A-TRA) 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 Go/Gi 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 hyperphos- phorylated 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.