The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, Nangang District, Harbin, 150086, China.
Dig Dis Sci. 2013 Jun;58(6):1590-601. doi: 10.1007/s10620-012-2539-z. Epub 2013 Feb 3.
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.
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.
ShRNA plasmids targeting survivin and CD44v3 were singly or co-transfected into SW480 cells.
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).
These results suggest combined transfection of survivin shRNA and CD44v3 shRNA may produce a synergistic effect on gene therapy in colorectal cancer.
结直肠癌是人类常见的恶性肿瘤之一,其发病率逐年逐渐升高。Survivin 和 CD44v3 在结直肠癌细胞中过度表达,是基因治疗的理想靶点。研究表明,下调 survivin 可促进细胞凋亡,抑制细胞增殖,降低 CD44v3 的表达可抑制肿瘤的侵袭能力。但难以达到满意的治疗效果。
本研究采用 survivin 和 CD44v3 短发夹 RNA(shRNA)联合转染结直肠癌细胞系 SW480,观察其对细胞凋亡、增殖和侵袭能力的影响。
将靶向 survivin 和 CD44v3 的 shRNA 质粒单独或共转染至 SW480 细胞。
共转染组对细胞生长的抑制作用最显著(P<0.05),细胞凋亡率最高(P<0.05),侵袭能力最低。裸鼠移植瘤模型中,共转染组的肿瘤抑制率明显高于其他各组(P<0.05)。此外,共转染组的微血管密度明显低于其他各组(P<0.05)。
提示 survivin shRNA 与 CD44v3 shRNA 联合转染可能对结直肠癌的基因治疗具有协同作用。