Tan Qiang, Ren Xiao-Yuan, Li Jing, Wang Fang, Deng Sheng-Ju, Zeng Hui-Hui
Department of Chemo-biology, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Ai Zheng. 2009 May;28(5):472-7.
The expression and activity of thioredoxin reductase (TrxR) are significantly higher in tumor tissues than in normal tissues, but the correlation of plasma TrxR activity to tumor growth has seldom been reported. This study was to evaluate the correlation of plasma TrxR activity to the growth of hepatocellular carcinoma (HCC) H22 cell xenografts in mice.
H22 cells were injected subcutaneously into Kunming mice to establish HCC model. The mice were divided into control group, mice group, low dose (36 mg/kg), moderate dose (72 mg/kg) and high dose (216 mg/kg) ethaselen groups. The mice in control group and model group were given 0.5% sodium carboxymethyl cellulose (CMC-Na). Blood samples were drawn before tumor cell inoculation, when tumor volume reached 100 mm3, and at Days 1, 4 and 10 of treatment. TrxR activity in plasma and tumor tissues was detected by dithio-bis-nitrobenzoic acid (DTNB) method.
The inhibition rates of tumor growth were 59.5% in low dose ethaselen group, 74.3% in moderate dose ethaselen group, and 74.9% in high dose ethaselen group. Plasma TrxR activity was stable in control mice, and was correlated positively to tumor volume in tumor-bearing mice. At the end of treatment, the inhibition rates of TrxR activity in plasma and tumor were 59.2% and 15.3% in low dose ethaselen group, 68.4% and 25.8% in moderate dose ethaselen group, 68.9% and 29.8% in high dose ethaselen group.
Plasma TrxR activity is correlated positively to tumor growth. Ethaselen can inhibit TrxR activity corresponding to tumor growth inhibition.
硫氧还蛋白还原酶(TrxR)在肿瘤组织中的表达及活性显著高于正常组织,但血浆TrxR活性与肿瘤生长的相关性鲜有报道。本研究旨在评估血浆TrxR活性与小鼠肝细胞癌(HCC)H22细胞异种移植瘤生长的相关性。
将H22细胞皮下注射到昆明小鼠体内建立HCC模型。将小鼠分为对照组、模型组、低剂量(36 mg/kg)、中剂量(72 mg/kg)和高剂量(216 mg/kg)乙硒半胱氨酸组。对照组和模型组小鼠给予0.5%羧甲基纤维素钠(CMC-Na)。在接种肿瘤细胞前、肿瘤体积达到100 mm3时以及治疗第1、4和10天采集血样。采用二硫代双硝基苯甲酸(DTNB)法检测血浆和肿瘤组织中的TrxR活性。
低剂量乙硒半胱氨酸组、中剂量乙硒半胱氨酸组和高剂量乙硒半胱氨酸组的肿瘤生长抑制率分别为59.5%、74.3%和74.9%。对照组小鼠血浆TrxR活性稳定,荷瘤小鼠血浆TrxR活性与肿瘤体积呈正相关。治疗结束时,低剂量乙硒半胱氨酸组血浆和肿瘤中TrxR活性的抑制率分别为59.2%和15.3%,中剂量乙硒半胱氨酸组分别为68.4%和25.8%,高剂量乙硒半胱氨酸组分别为68.9%和29.8%。
血浆TrxR活性与肿瘤生长呈正相关。乙硒半胱氨酸可抑制TrxR活性,相应地抑制肿瘤生长。