敲除TSPAN1抑制人结肠癌细胞的生长和侵袭

Knockout of TSPAN1 Inhibits Tumor Growth and Metastasis of Human Colon Cancer

目的 TSPAN1能够影响人结直肠癌细胞的增殖、扩散和侵袭。方法用腺病毒同源重组的方法建立TSPAN1缺失的人结直肠癌HCT116细胞系,CCK-8、克隆形成、划痕和Transwell实验分别检测缺失TSPAN1的细胞生长速率、成瘤、迁移和侵袭能力。裸鼠成瘤实验检测TSPAN1对肿瘤扩散的影响。双荧光素酶实验验证TSPAN1对雌激素受体和TGF-β受体活性的影响。结果缺失TSPAN1的HCT116细胞的生长速率、成瘤、迁移和侵袭能力显著降低。在裸鼠中分别注射野生型和缺失TSPAN1的HCT116细胞,后者肿瘤扩散变慢,并且裸鼠的成活率提高。过表达TSPAN1能够激活雌激素受体和TGF-β受体。结论 TSPAN1可能通过雌激素受体和TGF-β受体通路来调节细胞增殖和侵袭过程,并且为治疗结直肠癌提供了潜在的新靶标。

Objective TSPAN1 affects human colon tumor cells on proliferation, migration and invasion. Methods We established a TSPAN1 -deficient HCT116 cell line by adenovirus homologous recombination. Then we used CCK -8, colony formation, wound healing and Transwell assays to detect the rate of cell proliferation and the ability of tumor formation, migration and invasion of TSPAN1 - deficient cells. With nude mouse tumorigenicity assay, we also tested the effect of TSPAN1 on the spread of tumor. Dual luciferase experi- ment validated that TSPAN1 effected the activity of estrogen receptor and TGF - beta receptors. Results The rate of cell proliferation and the ability of tumor formation, migration and invasion were significantly reduced in TSPAN1 - deficient cells. We also injected HCT116 and TSPAN1 -deficient HCT116 ceils into athymic nude mice via the tail vein, and found a dramatic reduction of tumor cell migration. Mice injected with TSPAN1 - deficient cells showed prolonged survival. Overexpression of TSPAN1 could active estrogen receptor and transforming growth factor - β receptor. Conclusion TSPAN1 might regulate cell migration and invasion through these pathways. Thus, we suggest that TSPAN1 may be a novel therapeutic target for colon cancer treatment.