关键词: 低剂量, 有机硒, 细胞亚株, 异质性, 肿瘤细胞

Abstract:

As a synthesized antineoplastic organoselenium compound, ethaselen is known to induce apoptosis in tumor cells via dose-dependent thioredoxin reductase (TrxR) inhibition. Thioredoxin, the multifunctional biological substrate of TrxR, is then left in the oxidized state, which subsequently leads to intracellular accumulation of reactive oxygen species (ROS), cell cycle arrest and/or apoptosis. However, the low dose effect of ethaselen remains largely unknown. Several subclones have been derived from HepG2 cells by using single cell or colony isolation. The low dose of ethaselen was defined as the drug concentration of retaining >90% HepG2 cells alive. The HepG2 cells were used as reference of its subclones (SM01, SM02 and SM03), and the cell cycle transition, intracellular proteins change, colony formation and sphere growth were assayed in treatment of low dose ethaselen. HepG2 and its subclones differently responded to lethal dose of cisplatin or 5-fluorouracil. Low dose of ethaselen (1 µm) modulated the cell cycle transition at 12 h of treatment, but cells were partially recovered at 24 h of treatment though some proteins were still affected. Low dose of ethaselen did not inhibit the small colony (diameter >100 µm) formation and sphere growth of HepG2 and SM01. However, low dose of ethaselen could specifically inhibit the survival, large colony (diameter >500 µm) formation and sphere growth of SM03, although SM03 could be rapidly recovered from ethaselen-induced cell cycle check. HepG2 and its subclone cells could survive but respond differently to treatment of low dose ethaselen (1 µM). Low dose of ethaselen could significantly inhibit a HepG2 subclone (SM03) in cell survival and colony growth.

Key words: Low dose, Organoselenium, Cell subcloning, Heterogeneity, Tumor cell