[摘 要] 目的：探究花旗松素（TAX）通过Rac1/NF-κB/AKT信号通路调控人膀胱癌T24细胞的恶性生物学行为。方法：常规 培养膀胱癌T24细胞，将其分为：Ctrl组（未处理）、TAX-L组（5 μmol/L TAX处理）、TAX-M组（10 μmol/L TAX处理 ）、TAX-H组 （20 μmol/L TAX处理）、TAX-H + Rac1激活剂组（20 μmol/L TAX + 50 nmol/L ML-097处理）。CCK-8法、克隆形成实验、划痕愈合 实验、Transwell小室实验和流式细胞术分别检测不同浓度TAX对T24细胞增殖、迁移、侵袭能力和凋亡的影响，WB法检测对各 组T24细胞中细胞凋亡、上皮间充质转化、Rac1/NF-κB/AKT轴相关蛋白表达的影响；T24细胞裸鼠移植瘤实验检测TAX对移植 瘤生长的影响。结果：TAX呈剂量依赖性地抑制T24细胞的增殖、迁移和侵袭能力，并促进其凋亡（均P < 0.05），促进凋亡蛋 白BAX和E-cadherin、抑制Rac1/NF-κB/AKT 信号通路相关蛋白的表达、Bcl-2和N-cadherin蛋白表达（均P < 0.05），抑制移植 瘤的生长（P < 0.05），ML-097均可部分逆转上述作用（均P < 0.05）。结论：TAX通过抑制Rac1/NF-κB/AKT信号通路中抑制膀胱 癌T24细胞的恶性生物学行为，促进其凋亡。

[Abstract] Objective: To investigate the effect of toxifolin (TAX) on the malignant biological behaviors of human bladder cancer T24 cells through the Rac1/NF-κB/AKT signaling pathway. Methods: Bladder cancer T24 cells were routinely cultured and divided into: Ctrl group (untreated), TAX-L group (5 μmol/L TAX), TAX-M group (10 μmol/L TAX), TAX-H group (20 μmol/L TAX), and TAX-H+ Rac1 activator group (20 μmol/L TAX + 50 nmol/L ML-097). CCK-8 method, clone formation assay, scratch healing assay, Transwell chamber assay, and flow cytometry were used to evaluate the effects of different concentrations of TAX on the proliferation, migration, invasion, and apoptosis of T24 cells. WB method was used to examine the expression of apoptosis-related proteins, epithelial mesenchymal transition (EMT)-related proteins, and Rac1/NF-κB/AKT axis related proteins in T24 cells; A nude mice xenograft model was used to assess the effect of TAX on tumor growth. Results: TAX dose-dependently inhibited the proliferation, migration, and invasion of T24 cells and promoted apoptosis (all P < 0.05). TAX also increased the expression of apoptosis proteins BAX and E cadherin, while decreasing the expression of Bcl-2, N-cadherin, and Rac1/NF-κB/AKT signaling pathway-related proteins (all P < 0.05). Furthermore, TAX inhibited tumor growth in the xenograft model (P < 0.05). ML-097 partially reversed these effects (all P < 0.05). Conclusion: TAX inhibits the malignant biological behaviors of bladder cancer T24 cells and promotes their apoptosis by inhibiting Rac1/NF-κB/AKT signaling pathway.

河北省医学科学研究课题计划（No. 20220216）