[摘 要] 目的：探究人参皂苷Rg3（GRG3）通过调控PI3K/AKT/mTOR通路介导的磷酸戊糖途径（PPP）对乳腺癌（BC）细胞免 疫逃逸的影响。方法：常 规 培 养 MCF7 细 胞 ，将 其 分 为 对照组、GRG3 低剂量（GRG3-L）组、GRG3 高剂量（GRG3-H）组、 GRG3-H + 740Y-P（PI3K激活剂）组和Ly294002（PI3K抑制剂）组。克隆形成实验、流式细胞术、DCFH-DA荧光探针法和WB法 分别检测各组细胞的增殖、凋亡、ROS水平，以及PPP和PI3K/AKT/mTOR通路相关蛋白的表达。CCK-8法检测各组NK-92MI细 胞对MCF7细胞的杀伤率，ELISA检测各组MCF7细胞中CXCL-2、CXCL-8、G6PD和NADPH水平，以及共培养各组细胞培养基 中TNF-α、IFN-γ水平。结果：GRG3可抑制MCF7细胞的克隆形成能力（均P < 0.05），促进MCF7细胞的凋亡（均P < 0.05），抑制 MCF7细胞中CXCL-2、CXCL-8、G6PD、NADPH和ROS水平（均P < 0.05），抑制PPP和PI3K/AKT/mTOR信号通路（均P < 0.05）， 促进NK-92MI细胞分泌TNF-α和IFN-γ（均P < 0.05），提升NK-92MI细胞对MCF7细胞的杀伤率（均P < 0.05），上述作用均可被 740Y-P部分逆转（均P < 0.05）。结论：GRG3可通过抑制PI3K/AKT/mTOR通路介导的PPP来抑制乳腺癌MCF7细胞生物学行 为和免疫逃逸。

[Abstract] Objective: To investigate the effect of ginsenoside Rg3 (GRG3) on the immune escape of breast cancer cells by regulating pentose phosphate pathway (PPP) mediated by PI3K/AKT/mTOR signaling pathway. Methods: MCF7 cells were routinely cultured and divided into five groups: control group, GRG3 low-dose (GRG3-L) group, GRG3 high-dose (GRG3-H) group, GRG3-H + 740Y-P (PI3K activator) group, and Ly294002 (PI3K inhibitor) group. Colony formation assay, flow cytometry, DCFH-DA fluorescent probe assay, and WB were used to evaluate cell proliferation, apoptosis, ROS levels, and the expression of proteins related to the PPP and the PI3K/Akt/mTOR signaling pathway in each group, respectively. The cytotoxic effect of NK-92MI cells against MCF7 cells was measured using the CCK-8 assay. ELISA was employed to detect the levels of CXCL-2, CXCL-8, G6PD, and NADPH in MCF7 cells, as well as the levels of TNF-α and IFN-γ in the culture supernatant of co-cultured cells. Results: GRG3 significantly suppressed the clonogenic ability of MCF7 cells (all P < 0.05), promoted apoptosis of MCF7 cells (all P < 0.05), and reduced the levels of CXCL-2, CXCL-8, G6PD, NADPH, and ROS in MCF7 cells (all P < 0.05). Additionally, GRG3 inhibited the PPP and PI3K/Akt/mTOR signaling pathways (all P < 0.05), promoted the secretion of TNF-α and IFN- γ by NK-92MI cells (all P < 0.05), and enhanced the cytotoxicity of NK-92MI cells against MCF7 cells (all P < 0.05). These effects were partially reversed by 740Y-P (P < 0.05). Conclusion: GRG3 inhibits the biological behavior and immune escape of breast cancer MCF7 cells by suppressing the PI3K/AKT/ mTOR pathway-mediated PPP.

[基金项目] 武汉市卫健委中医药科研项目（No. WZ24B58）