Anti-tumor effect of Ad/Bcl-XL shRNA on colorectal cancer xenografts derived from patient tumors

OBJECTIVE: To establish a specific colorectal cancer xenografts derived from patient tumors, and further detect the anti-cancer effect of Ad/Bcl-XL shRNA on these xenografts. METHODS: Firstly, we established the rectal cancer xenografts by using the fresh operation specimen of patients with colorectal cancer. Then these xenografts were treated with Ad/Bcl-XL shRNA. Ad/GFP and PBS were used as control groups. After treatment, we monitored the tumor size, detected the apoptosis of tumor tissue and the side effect on normal organs and also recorded the survival time. RESULTS: Three palpable tumors come out from 22 inoculations, which were named as NO. 9, NO. 15, and NO. 18, respectively. Histologically, they were similar with the original tumor of corresponding patient. Our results demonstrated that Ad/Bcl-XL shRNA could effectively suppress the tumor growth in all three colorectal cancer xenografts. The tumor volume of Ad/Bcl-XL shRNA group in model NO. 9 was (351.4±108.4) mm³, whereas the tumor volume of Ad/GFP group and PBS group were (666±103.6) and (677.3±252.6) mm³ respectively (H=8.06, P=0.018). In model NO. 15, the tumor volume of Ad/Bcl-XL shRNA group was (240.4±83.3) mm³, whereas the tumor volume of Ad/GFP group and PBS group were (474.4±44.4) and (559.9±118.4) mm³, respectively (F=19.409, P<0.001). In model NO. 18, the tumor volume of Ad/Bcl-XL shRNA group was (230.5±187.9) mm³, whereas the tumor volume of Ad/GFP group and PBS group were (619±139.7) and (668.7±246.6) mm³, respectively (F=8.966, P=0.003). Subsequent TUNEL assay indicated that Ad/Bcl-XL shRNA induced obvious apoptosis in tumor tissue, the ratio reached to 10.98% which was significantly higher than that of Ad/GFP (1.47%) or PBS group (1.52%), (H=9.38, P=0.009). Our data also showed that Ad/Bcl-XL shRNA prolonged the survival time of nude mice. The over survival of PBS, Ad/GFP and Ad/Bcl-XL shRNA groups in model NO. 9 were 31, 31.4 and 58 d (P=0.009). In Model NO. 15 and NO. 18, they were 75.3, 84.3, 99 d (P=0.014), and 33.4, 33.6, 72.8 d (P=0.046), respectively. CONCLUSIONS: Our data shows that Ad/Bcl-XL shRNA have effective anti-tumor effects on the colorectal cancer xenografts derived from patient tumor, suggesting it can be a potential way for colorectal cancer treatment.