Zhonghong Liu1, Yonghang Guo, Juan Li, Jun Xu, Bingrong Liu. 1. The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin, 150086, China. zhaoyy@sj-hospital.org
Abstract
INTRODUCTION: Colorectal cancer is one of the common malignant tumors in humans, and the incidence rate is gradually increasing year by year. Survivin and CD44v3 are ideal targets for gene therapy due to their overexpression in colorectal cells. Studies show that downregulation of survivin could promote apoptosis and depress proliferation, and reduction of CD44v3 expression could inhibit tumor invasive capacity. It is difficult to achieve satisfactory curative effect. OBJECTIVE: In this study, we use survivin and CD44v3 short hairpin RNAs (shRNA) combined transfection into colorectal cancer cell line SW480 to investigate its effects on the cell apoptosis, proliferation and invasiveness. METHODS: ShRNA plasmids targeting survivin and CD44v3 were singly or co-transfected into SW480 cells. RESULTS: The co-transfection group exhibited the most significant inhibitory effect on cell growth (P < 0.05) and the highest apoptosis rate (P < 0.05). In addition, the invasive capacity in the co-transfected group was the least. The tumor inhibition rate of the cotransfected group in xenograft tumor mice was significantly higher than other groups (P < 0.05). Moreover, the microvessel density of the co-transfected group was significantly decreased compared with other groups (P < 0.05). CONCLUSION: These results suggest combined transfection of survivin shRNA and CD44v3 shRNA may produce a synergistic effect on gene therapy in colorectal cancer.
INTRODUCTION:Colorectal cancer is one of the common malignant tumors in humans, and the incidence rate is gradually increasing year by year. Survivin and CD44v3 are ideal targets for gene therapy due to their overexpression in colorectal cells. Studies show that downregulation of survivin could promote apoptosis and depress proliferation, and reduction of CD44v3 expression could inhibit tumor invasive capacity. It is difficult to achieve satisfactory curative effect. OBJECTIVE: In this study, we use survivin and CD44v3 short hairpin RNAs (shRNA) combined transfection into colorectal cancer cell line SW480 to investigate its effects on the cell apoptosis, proliferation and invasiveness. METHODS: ShRNA plasmids targeting survivin and CD44v3 were singly or co-transfected into SW480 cells. RESULTS: The co-transfection group exhibited the most significant inhibitory effect on cell growth (P < 0.05) and the highest apoptosis rate (P < 0.05). In addition, the invasive capacity in the co-transfected group was the least. The tumor inhibition rate of the cotransfected group in xenograft tumormice was significantly higher than other groups (P < 0.05). Moreover, the microvessel density of the co-transfected group was significantly decreased compared with other groups (P < 0.05). CONCLUSION: These results suggest combined transfection of survivin shRNA and CD44v3 shRNA may produce a synergistic effect on gene therapy in colorectal cancer.