[Mechanism of arsenic trioxide induced apoptosis in cultured human lens epithelium cells].
摘要
OBJECTIVE: To study cytotoxic effects of arsenic trioxide (As2O3) on the human lens epithelium cells and to identify the biological mechanism for these effects. METHODS: In this experimental study, human lens epithelium cells (FHL124 cells) were cultured in Eagle's minimum essential medium supplemented with 5% fetal calf serum. The effects of As2O3 on FHL124 cells growth were tested by MTT, and apoptosis was detected by TUNEL assay. Gene changes were detected by real-time PCR (Taqman). As2O3-induced changes in cell calcium level were measured by real-time fluorometric single-cell digital imaging techniques after Fura-2 incorporation. RESULTS: As2O3 inhibited the growth of FHL 124 cells in vitro in a dose-dependent manner, given an IC50 value of 1.5 micromol/L. As2O3 induced apoptosis of FHL124 cells as showed by TUNEL assay. As2O3 provoked an endoplasmic reticulum (ER) stress response identified through an up regulation of EIF2A, ERN1 and ATF6 (F = 8.51, P = 0.0005). As2O3 depleted the calcium store and consequently lead to a decrease of calcium signaling (P = 0.0018). Moreover, As2O3 had a moderate effect on the calcium influx pathway. CONCLUSIONS: As2O3 inhibits the growth and induces apoptosis of human lens epithelium cells. As2O3 provokes an ER stress which could be the cause of apoptic processes.