硫酸右旋糖苷对宫颈癌细胞迁移、侵袭的影响及其分子机制

目的探讨硫酸右旋糖苷(DS)对宫颈癌细胞迁移、侵袭及上皮间质转化(EMT)的影响,并探讨其作用机制。方法取宫颈癌Hela细胞,分别加入0、0.1%、0.3%、0.6%、1%的DS处理,采用CCK-8增殖实验筛选DS的最佳作用浓度和最佳作用时间分别为0.3%和48 h,选择该浓度与作用时间进行后续实验。将Hela细胞分为对照组、DS组、DS+740Y-P组,对照组仅加入完全培养基,DS组加入0.3%DS,DS+740Y-P组加入0.3%DS和20μmol/L PI3K激动剂740Y-P,分别培养48 h。采用划痕愈合实验检测细胞迁移能力,Transwell侵袭实验检测细胞侵袭能力,Westernblotting法检测细胞PI3K/AKT信号通路相关蛋白p-AKT、AKT(以p-AKT/AKT值表示通路活性)及EMT相关蛋白E-cadherin、Vimentin蛋白表达。结果与对照组相比,DS组细胞迁移率降低,穿膜细胞数减少,细胞中p-AKT/AKT、Vimentin蛋白表达水平降低,E-cadherin蛋白表达水平升高(P均<0.05)。与DS组相比,DS+740Y-P组细胞迁移率升高,穿膜细胞数增多,细胞p-AKT/AKT蛋白、Vimentin蛋白表达水平升高,E-cadherin蛋白表达水平降低(P均<0.05)。结论DS能够抑制宫颈癌Hela细胞的迁移和侵袭能力,其机制可能是通过PI3K/AKT信号通路调控EMT从而发挥抑制肿瘤作用。

Roles of Rap1 signaling in tumor cell migration and invasion

Ras-associated protein-1 （Rapl）, a small GTPase in the Ras-related protein family, is an important regulator of basic cellular functions （e.g., formation and control of cell adhesions and junctions）, cellular migration, and polarization. Through its interaction with other proteins, Rapl plays many roles during cell invasion and metastasis in different cancers. The basic function of Rapl is straightforward; it acts as a switch during cellular signaling transduction and regulated by its binding to either guanosine triphosphate （GTP） or guanosine diphosphate （GDP）. However, its remarkably diverse function is rendered by its interplay with a large number of distinct Rap guanine nucleotide exchange factors and Rap GTPase activating proteins. This review summarizes the mechanisms by which Rap 1 signaling can regulate cell invasion and metastasis, focusing on its roles in integrin and cadherin regulation, Rho GTPase control, and matrix metalloproteinase expression.