Space Medicine & Medical Engineering  2008;21(1):1-5

Chronotherapy by Ribozyme Targeted to Telomerase in Nude Mice with a Transplanted Tumor: Model for Human Hepatic Cancer

Yi QU ; Zhengrong WANG ; Chaomin WAN ; Xiang HUANG ; Dezhi MU ; Cornelissen GERMAINE ; Halberg FRANZ

Keywords

telomerase; ribozyme; chronotherapy; tumor

Country

China

Language

Chinese

Abstract

Objective To investigate therapeutic autcomes of using telomerase inhibitors to treat cancer at the presumably most and least opportune circadian stages basing on our earlier study. Methods Twenty-four BALB/C nude mice were synchronized to a regimen of LD12:12 for 4 wk. Hepatic cancer cells (SMMC-7721) were implanted into both flanks of each mouse.Two weeks after transplantation,the hTERT-5'RZ was used to treat the hepatic cancer transplanted into the nude mice daily for two weeks,the injection times being either 9 or 21 HALO.Results The tumorinhibition ratio of mice treated at 21 HALO (65%) was statistically significantly higher than that of mice treated at 9 HALO (48%). Telomerase activity was also reduced to a greater extent in mice treated withhTERT-5'RZ at 21 than at 9 HALO, that was at the time of maximal circadian telomerase activity. Conclusion Injection of ribozyme targeted to telomerase during the tumor's DNA synthesis is associated with a betterinhibition of tumor growth and a better therapeutic outcome in hepaticcancer.