[摘 要] 目的：探究重楼皂苷Ⅱ（PPⅡ）抑制甲状腺癌（TC）恶性生物学行为的分子机制。方法：常规培养甲状腺癌细胞TPC1，实验分为sh-NC、sh-可溶性半乳糖凝集素3（sh-LGALS3）、OE-NC、OE-LGALS3和 OE-LGALS3 + PPⅡ组，用转染试剂将应用质粒转染至各组TPC1细胞中。qPCR法检测TPC1细胞中LGALS3 mRNA的表达，WB法检测各组TPC1细胞中LGALS3、PI3K/AKT信号通路相关蛋白的表达，CCK-8法、Transwell实验、划痕愈合实验和流式细胞术分别检测各组TPC1细胞增殖、迁移和侵袭能力，以及细胞凋亡情况。结果：PPⅡ抑制TPC1细胞的增殖、迁移和侵袭，并诱导其凋亡（均P < 0.000 1）。数据库数据分析显示LGALS3在甲状腺癌组织中高表达（P < 0.001）且是PPⅡ的靶基因。LGALS1在TPC1细胞中呈高表达（P < 0.000 1），敲减LGALS3抑制TPC1细胞的恶性生物学行为，并促进其凋亡（均P < 0.000 1），PPⅡ通过抑制LGALS3 mRNA和蛋白的表达（P < 0.01或P < 0.001）从而抑制TPC1细胞的恶性生物学行为（P < 0.01或P < 0.000 1），PPⅡ抑制LGALS3表达抑制PI3K/AKT信号通路的激活水平（P <0.001或P <0.000 1），LGALS3通过PI3K/AKT信号通路促进TPC1细胞的恶性生物行为（P < 0.000 1）。结论：PPⅡ通过抑制TPC1细胞中LGALS3的表达，缓解PI3K/AKT信号通路的过度激活从而发挥抑癌作用。

Objective: To investigate the molecular mechanism of lncRNA FOXD2-AS1 participating in apatinib resistance in gastric cancer cells by regulating miR-185-5p/CCND2 axis. Methods: The gastri cancer tissues and corresponding paracancerous tissues of 25 patients with gastric cancer were collected from April 2016 to December 2017 in the Fifth People’s Hospital of Wuxi City. The expressions of FOXD2-AS1, miR-185-5p, and cyclin D2 (CCND2) in gastric cancer tissues or cell lines were examined by quantitative realtime polymerase chain reaction (qRT-PCR). CCK-8 assay, Transwell assay and Annexin V-FITC/PI double staining flow cytometry assay were applied to assess the sensitivity of gastric cancer cells to apatinib. The interaction between FOXD2-AS1, miR-185-5p and CCND2 was explored by dual luciferase reporter gene assay, which was then confirmed by qRT-PCR, and Western blotting. Results: FOXD2-AS1 was highly expressed in gastric cancer tissues and apatinib-resistant gastric cancer cells. Over-expression of FOXD2-AS1 promoted apatinib-resistance of MGC-803/AP cells. Dual luciferase reporter gene assay confirmed that FOXD2-AS1 directly interacted with miR-185-5p and suppressed its expression. miR-185-5p significantly abolished the promotion effect of FOXD2-AS1 on apatinibresistance via inhibiting cell proliferation, invasion and promoting apoptosis of gastric MGC-803/AP cells. miR-185-5p could negatively regulate CCND2 expression; and FOXD2-AS1 promoted the cell proliferation, invasion and inhibited apoptosis of MGC-803/AP cells via down-regulating the inhibition effect of miR-185-5p on CCND2, thus further enhanced the apatinib-resistance of gastric cancer cells. Conclusion: FOXD2-AS1 induced apatinib-resistance of gastric cancer cells by regulating miR-185-5p/CCND2 axis.