氧胁迫对人肝癌细胞生长分化和凋亡的影响

EFFECTS OF OXIDATIVE STRESS ON THE PROLIFERATION, DIFFERENTIATION AND APOPTOSIS IN THE HUMAN HEPATOMA CELLS

采用不同浓度的抗坏血酸(50—800μmol/L)和硫酸亚铁(2.5—40μmol/L)系统生成以羟自由基为主的各种程度氧胁迫,使之作用于人肝癌细胞。本文所采用的不同程度的氧胁迫均能抑制癌细胞的生长。低水平氧胁迫可使肝癌细胞失去某些恶性特征,趋向分化,表现为细胞表面对Con-A的凝集力、甲胎蛋白含量、γ-谷氨酰转肽酶和酪氨酸-α-酮戊二酸转氨基酶活性都朝着分化方向变化,差异显著。分化后的细胞克隆形成能力显著降低。在分化过程中,出现一定量的凋亡细胞。随着氧胁迫程度的增高,凋亡细胞增多,表现为非贴壁细胞增多,细胞体积变小,染色质凝缩在核膜边缘,呈新月形,核碎裂,但质膜完整。细胞核中DNA降解成大约21.2kbp大小的大片段DNA。有望通过严格控制氧胁迫程度来减慢肝癌细胞增殖,促进分化和凋亡,使恶性细胞逆转成良性细胞。

The human hepatoma cells SMMC-7721 were treated with different concentrations of ascorbic acid (50-800μmol/L) and FeSO4(2.5-40μmol/L)system to generate oxidative stress at various degrees. The oxidative stress induced by the system were mainly contributed to hydroxyl radical. All the various degrees of oxidative stress in this study are able to inhibit the proliferation of hepatoma cells. While low levels of oxidative stress may cause hepatoma cells lost some malignant features, such as aggregation of Con-A to the cell surface, α-fetoprotein,γ-glutamyl-transepeptidase and tyrosine -α-ketoglutarate transaminase, all of the 4 indices tended to cell differentiaton, coloning efficiency potential decreased significantly, and apoptotic cells appeared. The numbers of apoptotic cells increased with the increasing of oxidative stress. The apoptotic cells exhibited non-adherent, smaller, chro-matin condensed around the periphery of the nucleus in the shape of crescent, nuclear fragmentations but with intact cellular membrane, and DNA degraded to around 21. 2 kbp fragment. All of the results showed that there is possibility to inhibit hepatoma cells growth, to promote differentiation and apoptosis, and therefore to initiate reverse transformation via strict regulation of ox-diative stress.