Lee Chang-Yin, Hsu Yi-Chao, Wang Jir-You, Chen Chien-Chih, Chiu Jen-Hwey
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, Republic of China.
Liver Int. 2008 Jul;28(6):841-55. doi: 10.1111/j.1478-3231.2008.01698.x.
BACKGROUND/AIMS: Oxidative DNA damage by reactive oxygen species is involved in the process of liver carcinogenesis. To test the hypothesis that a remedy containing Scutellaria baicalensis Georgi (Sb) and Bupleurum scorzonerifolfium Willd (Bs) (Sb/Bs remedy) modulates hepatic neoplastic growth, BOP (N-nitrosobis(2-oxopropyl)amine)-induced liver cancers in hamsters were established.
Parameters such as survival rate, tumour area, tumour foci, 8-hydroxydeoxyguanosine (8-OHdG), caspase-3, transforming growth factor (TGF-beta1) and tumour necrosis factor-alpha (TNF-alpha) were measured after Sb/Bs remedy treatment during BOP-induced carcinogenesis.
The results showed that the Sb/Bs remedy and its constituents Sb and Bs suppressed the tumour area in BOP-induced liver tumours. Because selenium (Sel) is toxic at a high dose (10 mg/kg), with a low survival rate (0%), the combination of Sb/Bs remedy and low-dose Sel (1 mg/kg) was found to decrease the tumour area and the number of tumour foci while increasing serum TNF-alpha and TGF-beta1, but not IL-6 levels. Besides, the Sb/Bs remedy, when combined with low-dose Sel, not only decreased the expression of 8-OHdG and increased caspase-3 expression within the glutathione S-transferase placental form-positive tumour foci but also increased tumour apoptosis in BOP-induced hamsters.
We conclude that low-dose Sel has a chemoprevention effect on BOP-induced liver tumours and such an effect was more enhanced when combined with Sb/Bs treatment.
背景/目的:活性氧引起的氧化性DNA损伤参与肝癌发生过程。为验证含黄芩(Sb)和柴胡(Bs)(Sb/Bs制剂)的药物调节肝脏肿瘤生长这一假说,建立了N-亚硝基双(2-氧代丙基)胺(BOP)诱导的仓鼠肝癌模型。
在BOP诱导致癌过程中,用Sb/Bs制剂处理后,测定生存率、肿瘤面积、肿瘤灶、8-羟基脱氧鸟苷(8-OHdG)、半胱天冬酶-3、转化生长因子(TGF-β1)和肿瘤坏死因子-α(TNF-α)等参数。
结果显示,Sb/Bs制剂及其成分Sb和Bs可抑制BOP诱导的肝肿瘤的肿瘤面积。由于高剂量(10 mg/kg)的硒(Sel)具有毒性,生存率低(0%),因此发现Sb/Bs制剂与低剂量Sel(1 mg/kg)联合使用可减小肿瘤面积和肿瘤灶数量,同时提高血清TNF-α和TGF-β1水平,但不提高白细胞介素-6水平。此外,Sb/Bs制剂与低剂量Sel联合使用时,不仅可降低谷胱甘肽S-转移酶胎盘型阳性肿瘤灶内8-OHdG的表达并增加半胱天冬酶-3的表达,还可增加BOP诱导的仓鼠的肿瘤凋亡。
我们得出结论,低剂量Sel对BOP诱导的肝肿瘤具有化学预防作用,与Sb/Bs联合治疗时这种作用会更强。