Effects of treatment with platinum azidothymidine and azidothymidine on telomerase activity and Bcl-2 concentration in hepatocellular carcinoma- induced rats

ABSTRACT

Telomerase activity increases in cancer cells. Bcl-2 is an antiapoptotic factor that its concentration grows in many cancer cells including hepatocellular carcinoma cells. In this study, an attempt was made to investigate the effects of a new synthetic compound, platinum azidothymidine [Pt-AZT] on treatment of rats with Hepatocellular Carcinoma [HCC] and to compare its effects with azidothymidine [AZT] in alteration of telomerase activity and Bcl-2 concentration in HCC. Healthy adult male Wistar rats [n=100] were randomly divided into 4 groups [A, B, C, and D]. Group A contained 25 healthy rats and was considered as the control group. Liver preneoplastic lesions were induced in remaining animals [n=75] using Solt-Farber resistant hepatocyte protocol. These animals were randomly allocated in groups B, C and D. Group B was negative control [untreated], groups C and D were treated by intraperitoneal injection [IP] of Pt-AZT [0.9 mg/kg/day] and AZT [0.3 mg/kg/day], respectively for 14 days. After the treatment period, telomerase activity and Bcl-2 concentration were determined in the rats' liver. No HCC was developed in group A, but tumors were present in all other groups. Telomerase activity and Bcl-2 concentration were significantly lower in group C compared to groups B [0.159 +/- 0.06 vs. 0.577 +/- 0.116 IU/L, p<0.001, respectively and 0.931 +/- 0.388 vs. 3.94 +/- 0.74 ng/ml, p<0.001, respectively]. Similar results were observed in comparison with group D [0.331 +/- 0.06 vs. 0.577 +/- 0.116 IU/L, p<0.001, respectively and 0.931 +/- 0.388 vs. 2.94 +/- 0.594 ng/ml, respectively]. There was a significant negative correlation between telomerase activity and Bcl-2 concentration only in untreated cancer group [p=0.034]. In this study, higher anticancer activity of Pt-AZT in comparison to AZT was demonstrated. It effectively inhibits the growth of liver tumor in rats through extending apoptosis