摘要
瞄准：学习三氧化二砷的 anti-hepatoma 效率(作为(2 ) O (3 )) 在试验性的老鼠肝细胞的治疗，癌(HCC ) 由 2-acetamidofluorene (2-FAA ) 导致了并且阐明可能的机制。方法：SD 老鼠(2 瞬间旧) 用 2-FAA 被喂了让 8 wk 导致 HCC，然后他们被对待与作为(2 ) O (3 ) 或妈三倍。在 d 上 29，老鼠被打死，肝被称，肝肿瘤被数。肝织物的组织学的变化在显微镜下面被观察，并且细胞的动态参数被流动血细胞计数学习。Immunohistochemistry (二拍子的圆舞方法) 被用来在连续的节上观察脉管的内皮生长因素(VEGF ) 和微容器的密度(MVD ) 的表示。病理学的参数也被分析，浆液 aspartate aminotransferase (著名计算机生产厂商) 的层次，丙氨酸 aminotransferase (中高音) ，全部的胆红素(TBi ) ，和直接胆红素(DBi ) 。结果：肝肿瘤的数字在对待与的组显著地减少了作为(2 ) O (3 ) ，在特别中等剂量(1 mg/kg ) 组织(t = 2.80， P【0.01 ) 。当(2 ) O (3 ) 经由 apoptosis 引起了 HCC 细胞死亡；坏死被看见，当剂量是 1 mg/kg 时， apoptosis 是普通的。增长索引严厉地减少了在中等剂量(1 mg/kg ) 组织(7.87+/-4.11 对 24.46+/-6.49， t = 2087， P【0.01 ) ，然而并非在 0.2 mg/kg 组。然而，S阶段部分在两个组戏剧性地减少了，仅仅当剂量与控制相比是 1 mg/kg 时，它到达了底部水平( 0.40+/-0.13 对 3.01+/-0.51 ， t = 2.97 ， P【0.01 )，并且它显然在 G ( 0 ) /G ( 1 )( G ( 0 ) /G ( 1 )限制)伴有房间的累积。VEGF 和 MVD 在的表情中等剂量(1 mg/kg ) 组比生理盐水组显著地低(0.63+/-0.74 对 2.44+/-0.88， P【0.05；15.75+/-3.99 对 47.44+/-13.41， t = 2.80， P【0.01 ) 。与生理盐水组相比，是的中等剂量、低剂量的组( 2 ) O ( 3 )和妈三倍在浆液降低了中高音的层次( 61.46+/-9.46 ， 63.75+/-20.40 ， 61.18+/-13.00 对 108.98+/-29.86 ， t = 2.14 ， P【0.05 )，但是没有浆液著名计算机生产厂商诚实的效果， TBi ，和 DBi 。结论：当(2 ) O (3 ) 穿上禁止的效果，在老鼠的试验性的 HCC 的生长由 2-FAA 导致了，但是没在正常肝细胞上有明显的效果。机制可以通过堵住 VEGF 在血管生成上包含两极分裂，在 /G (1 ) 分阶段执行的 G (0 ) 的房间的累积，肿瘤房间的 apoptosis，和禁止的效果的减少。
AIM： To study the anti-hepatoma efficiency of arsenic trioxide （As2O3） in the treatment of experimental rat hepatocellular carcinoma （HCC） induced by 2-acetamidofluorene （2-FAA） and to elucidate the possible mechanisms.
METHODS： SD rats （2 mo old） had been fed with 2-FAA for 8 wk to induce HCC, and then they were treated with As2O3 or matrine. On d 29, the rats were killed and the liver was weighed and liver tumors were counted. The histological changes of liver tissue were observed under microscope, and the cellular dynamic parameters were studied by flow cytometry. Immunohistochemistry （two-step method） was used to observe the expression of vascular endothelial growth factor （VEGF） and micro-vessel density （MVD） on consecutive sections. The pathological parameters were also analyzed, the levels of serum aspartate aminotransferase （AST）, alanine aminotransferase （ALT）, total bilirubin （TBi）, and direct bilirubin （DBi）.
RESULTS： The number of liver tumors decreased significantly in groups treated with As2O3, especially in medium-dose （1 mg/kg） group （t = 2.80, P〈0.01）. As2O3 caused HCC cell death via apoptosis; necrosis was seen and apoptosis was common when the dose was 1 mg/kg. Proliferation index decreased sharply in medium-dose （1 mg/kg） group （7.87±4.11 vs24.46±6.49, t= 2087, P〈0.01）, but not in 0.2 mg/kg group. However, S-phase fraction decreased dramatically in both groups, it reached the bottom level only when the dose was i mg/kg compared with control （0.40±0.13 vs3.01±0.51, t= 2.97, P〈0.01）, and it was obviously accompanied with accumulation of cells in G0/G1 （G0/G1 restriction）. The expressions of VEGF and MVD in medium-dose （1 mg/kg） group were significantly lower than normal saline group （0.63±0.74 vs2.44±0.88, P〈0.05; 15.75±3.99 vs47.44±13.41, t= 2.80, P〈0.01）. Compared with normal saline group, mediumand low-dose groups As203 and matrine lowered the levels of ALT in serum （61.46±9.46, 63.75±20.40, 61.18±13.00 vs 108.98±29.86, t= 2.14, P〈0.05）, but had no effect onthe level of serum AST, TBi, and DBi.
CONCLUSION： As203 had inhibitory effect on growth of experimental HCC in rats induced by 2-FAA, but had no obvious effect on normal hepatic cells. The mechanisms may involve decrease of cell division, accumulation of cells in G0/G1 phase, apoptosis of tumor cells, and inhibitory effect on angiogenesis through blocking VEGF.
