[Correlation of plasma thioredoxin reductase activity to growth of H22 hepatocellular carcinoma xenografts in Kunming mice].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Plasma TrxR activity is correlated positively to tumor growth. Ethaselen can inhibit TrxR activity corresponding to tumor growth inhibition.
Tan
Qiang
Q
Department of Chemo-biology, School of Pharmaceutical Sciences, Peking University, Beijing, China.
Ren
Xiao-Yuan
XY
Li
Jing
J
Wang
Fang
F
Deng
Sheng-Ju
SJ
Zeng
Hui-Hui
HH
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors* / Q000097:blood* / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
C478160:(1,2-bis(1,2-benzisoselenazolone-3(2H)-ketone))ethane; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D016566:Organoselenium Compounds; D013880:Thioredoxin-Disulfide Reductase