三氧化二砷对人舌鳞癌细胞CAL-27侵袭能力的影响

The effect of arsenic trioxide on invasion of human tongue squamous carcinoma cell line CAL-27

目的检测三氧化二砷对人舌鳞癌细胞CAL-27体内、外侵袭能力的影响并探讨其相关作用机制。方法体外采用黏附实验、划痕实验、Transwell侵袭实验、免疫荧光染色和蛋白质印迹法检测三氧化二砷对CAL-27细胞黏附、迁移及侵袭能力的影响;体内采用免疫组织化学和蛋白质印迹法检测三氧化二砷对裸鼠移植瘤中CD44和基质金属蛋白酶(MMP)-2和MMP-9表达的影响。结果三氧化二砷作用后,实验组CAL-27细胞的黏附、迁移及侵袭能力明显低于对照组(P<0.05),细胞骨架微丝解聚,微管结构模糊、紊乱,MMP-2和MMP-9的表达下降;三氧化二砷降低了裸鼠移植瘤中CD44、MMP-2和MMP-9的表达。结论低浓度的三氧化二砷可降低人舌鳞癌细胞CAL-27细胞黏附能力,改变细胞骨架排列,下调CD44、MMP-2和MMP-9的表达,进而抑制癌细胞的侵袭能力。

Objective To study the effect of arsenic trioxide on the invasion of human tongue squamous carcinoma cell line CAL-27 in vitro and in vivo and explore the underlying mechanisms. Methods Adhesion assay, Transwell chamber membrane invasion culture system, immunofluorescence and Western Blot were performed to detect the effect of arsenic trioxide on adhesion, migration and invasion of CAL-27 cells in vitro. Immunohistochemical and Western Blot assays were used to study the protein levels of CD44, matrix metalloproteinases（MMP）-2 and MMP-9 in vivo. Results In vitro, arsenic trioxide at lower-dose could significantly reduce abilities of CAL-27 cells to adhere, migrate and invade（P〈0.05）; the depolymerization of microfilaments was observed and fuzzy and discontinuous arrangements of microtubules were visualized upon arsenic trioxide treatment. In addition, the cells treated with lower-dose arsenic trioxide displayed reduced protein expressions of CD44, MMP-2 and MMP-9 in vivo. Conclusion Arsenic trioxide at lower-dose could inhibit the ability of the CAL-27 cell to invade by inhibiting cellular adhesion, modulating cytoskeleton and reducing the protein expressions of CD44, MMP-2 and MMP-9.