Azidothymidine treatment of hepatocellular carcinoma in rats: an in vivo study of telomerase inhibition.
OBJECTIVE
Telomerase activation contributes to hepatocarcinogenesis. We designed an animal study to investigate the effect and possible mechanisms of treatment with telomerase inhibitor on HCC in a rat model.


METHODS
Adult male LEW/SsN rats were divided into 3 groups (n=60). Group A as the control. Groups B and C were given diethylnitrosamine (DEN), 5mg/kg/day. In addition, Group C rats received an intraperitoneal injection of 3'-azido2,3'dideoxythymidine azidothymidine (AZT), 0.3mg/kg/day for 14 days starting on week 18. Ten animals in each group were sacrificed at 18, 20, 22 and 24 weeks to evaluate the liver tumor. We compared telomerase mRNA, telomerase activity and Bcl-2 mRNA among the liver tissue of group A rats and tumor tissue of HCC from group B and C rats.


RESULTS
No HCC developed in group A, but tumors were present in group B and C rats by the 18th week. Group B's telomerase mRNA was significantly higher than group A's (p=0.009), but group C's was significantly higher than group A's (p=0.017) and lower than group B's (p=0.014). The same intergroup B vs. A and C vs. A relationship was also true for telomerase activity (p=0.009 and 0.009), but with no significant differences between group B and C (p=0.175).


CONCLUSIONS
AZT, the telomerase blocker, effectively inhibits the growth of liver tumor weight and decreases the metastasis score of HCC induced by DEN in rats in vivo.
Department of Surgery, Far Eastern Memorial Hospital, Taipei, Taiwan.
Kuo-Shyang
KS
Jeng
I-Shyan
IS
Sheen
Wen-Juei
WJ
Jeng
D000818:Animals; D019254:Genes, bcl-2; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D015215:Zidovudine / Q000627:therapeutic use*
D012333:RNA, Messenger; D015215:Zidovudine; D019098:Telomerase