Abstract:
ObjectiveTo discuss the effects of oncolytic adenovirus carrying human telomerase reverse transcriptase (hTERT) gene shRNA ZD55-double-hTERT on the growth of human prostatic cells in nude mice. MethodsBALB/C nude mice were subcutaneously inoculated with DU145 cells to establish a prostatic cell carcinoma model. Then, the tumor-bearing nude mice were intratumorally injected with ZD55-double-hTERT, ZD55-hTERT1, ZD55-hTERT2 and PBS respectively. The tumor size was measured at different time points. The expression of hTERT in tumor tissue was observed by laser scanning confocal microscopy and Western blotting. The apoptosis of tumor xenografts was measured by in situ end labeling technique (TUNEL). ResultsAfter seven weeks of treatment, the mean tumor size was (1841.5±182.3) mm3 for the PBS group, (689.0±93.5) mm3 for the ZD55-hTERT1 group, (669.2±84.3) mm3 for the ZD55-hTERT2 group, and (237.5±26.2) mm3 for the ZD55-double-hTERT group. Statistical difference was found between the ZD55-double-hTERT group, and ZD55-hTERT1 and ZD55-hTERT2 groups (P<0.01). The hTERT staining intensity was effectively reduced in tumor tissue from nude mice treated with ZD55-double-hTERT, compared with those in tumors treated with ZD55-hTERT1, ZD55-hTERT2 or PBS. The level of hTERT protein in the ZD55-double-hTERT group was statistically different from those in the ZD55-hTERT1 group (0.84±0.05), the ZD55-hTERT2 group (0.79±0.04) and the PBS group (1.25±0.07) (P<0.05). The apoptotic rate was (43.5±6.4)% in the ZD55-double-hTERT group, which was significantly higher than those in the other three groups (P<0.01). ConclusionsZD55-double-hTERT can more effectively inhibit the growth of tumor, which may be a novel tool for gene therapy of human prostatic cell carcinoma.