Therapeutic effect of oncolytic adenovirus ZD55-special AT rich sequence binding protein-1 expressing small hairpin RNA targeting special AT rich sequence binding protein-1 gene on implanted human prostate DU145 cell carcinoma in nude mice

Abstract

Objective To investigate the therapeutic effect of oncolytic adenovirus ZD55-special AT rich sequence binding protein-1 (SATB1) expressing small hairpin RNA targeting SATB1 gene on implanted human prostate DU145 cell carcinoma in nude mice. Methods When tumors reached 100-150 mm3, mice were divided randomly into four groups (8 mice for each group), which were treated by intratumoral injection of 100 μl of ZD55-SATB1, ZD55-enhanced green fluorescent protein (EGFP), Ad-SATB1 or phosphate buffer (PBS), respectively. Virus (5×108 pfu/d) was administered every other day for 3 times. The tumor was monitored every week by measuring tumor size for 49 days. At the end of the experiment, tumors were harvested for hematoxylin and eosin (HE) staining, immunohistochemistry and TdT-mediated dUTP nick end labeling (TUNEL) assay. Results The mean tumor size in ZD55-SATB1 group was (295.3±51.9) mm3, significantly smaller than that in ZD55-EGFP group (525.6±89.3) mm3 (P=0.017), Ad-SATB1 group (582.3±97.0) mm3 (P=0.010) and PBS group (777.1±139.8) mm3 (P=0.009). Lung tissues HE staining showed tumor metastasis was found in the lung of 8 nude mice in PBS group, two in ZD55-EGFP group, and none in ZD55-SATB1 group and Ad-SATB1 group. TUNEL showed that the apoptosis rate in ZD55-SATB1-treated group [(87.3±4.8)%] was significantly higher than that in ZD55-EGFP-treated group [(51.2±3.4)%, P=0.013], Ad-SATB1-treated group [(41.3±3.2)%, P=0.010] and PBS-treated group [(20.1±1.9)%, P=0.009] with the differences being statistically significant. SATB1 staining positivity was effectively reduced in tumor tissue in ZD55-SATB1 group [(13.8±1.2)] as compared with that in ZD55-EGFP group (81.1±7.3, P=0.010), Ad-SATB1 group (26.9±2.4, P=0.025) and PBS-treated group (88.3±7.8, P=0.009). Conclusion Oncolytic adenovirus ZD55-SATB1 has significant therapeutic effects on transplanted human prostate carcinoma in nude mice, suggesting that it may be a novel tool for gene therapy of human prostate carcinoma. Key words: Oncolytic adenovirus; Special AT rich sequence binding protein-1; Prostate carcinoma