论文部分内容阅读
作为一种合成的、有抗肿瘤活性的有机硒,乙烷硒啉可通过抑制硫氧还蛋白还原酶,导致其生物学底物硫氧还蛋白处于氧化状态,随后升高的细胞内活性氧引发细胞周期阻滞或触发凋亡。乙烷硒啉的低剂量作用尚未被研究。本研究中乙烷硒啉低剂量(1μM)定义为保持90%以上细胞存活的浓度。从单个HepG2细胞增殖而来的亚株(SM01,SM02,SM03)被用于低剂量乙烷硒啉效应检测。考察了低剂量乙烷硒啉对HepG2及其亚株的细胞周期转变、蛋白表达、集落形成、细胞球生长变化的影响。HepG2及其亚株对致死剂量的CDDP和5-FU显示了不同的敏感性。低剂量乙烷硒啉处理12h后S期比例升高,可在随后的12 h内部分恢复,其细胞内蛋白p53,NF-κB等尚未完全恢复。低剂量乙烷硒啉未抑制较小的细胞集落(直径>100μm)形成,未影响HepG2和SM01的细胞球生长。低剂量乙烷硒啉可显著抑制SM03细胞存活、较大细胞集落(直径>500μm)形成和细胞球生长,尽管SM03细胞蛋白水平恢复较快。总体上,HepG2及其亚株对与化学物和低剂量乙烷硒啉的反应不同,低剂量乙烷硒啉可抑制HepG2亚株(SM03)的存活和生长。
As a synthetic, antitumor activity of organic selenium, ethaselenol can inhibit thioredoxin reductase, leading to its biological substrate thioredoxin in an oxidized state, followed by increased intracellular reactive oxygen species Trigger cell cycle arrest or trigger apoptosis. The low dose of ethaselen has not been studied. Low doses of ethaselin (1 [mu] M) in this study were defined as concentrations that maintained more than 90% of cell survival. Sub-strains (SM01, SM02, SM03) that proliferated from a single HepG2 cell were used for the detection of low-dose ethaselen. The effects of low dose ethaselen on the cell cycle transformation, protein expression, colony formation and cell growth of HepG2 and its sub-strains were investigated. HepG2 and its sub-strains showed different sensitivities to lethal doses of CDDP and 5-FU. The proportion of S phase increased after 12 h treatment with low dose ethaselen, which could partially recover within 12 h, and the intracellular protein p53, NF-κB and so on were not completely restored. Low dose ethaselen did not inhibit the formation of smaller cell colonies (> 100 [mu] m in diameter) and did not affect the spheroplast growth of HepG2 and SM01. Low doses of ethaneselenol significantly inhibited the survival of SM03 cells, the formation of larger cell colonies (> 500 μm in diameter), and the growth of spheres, despite the rapid recovery of SM03 protein levels. Overall, HepG2 and its sub-strains respond differently to the chemotherapeutic agents and lower doses of ethaselen, and lower doses of ethaselen may inhibit the survival and growth of HepG2 sub-strain (SM03).