Department of Endoscopy, Huaihe Hospital of Henan University, Kaifeng 475000, Henan, China.
School of Basic Medical Sciences, Henan University, Kaifeng 475004, Henan, China.
Exp Mol Pathol. 2018 Dec;105(3):252-259. doi: 10.1016/j.yexmp.2018.08.011. Epub 2018 Aug 31.
Gastric cancer (GC) is a serious disease with high incidence rate and high mortality. Geniposide (GEN) exhibits multiple biological properties including anti-tumor function. However, effect of GEN on GC is not well studied. Hence, the effects of GEN on GC were investigated in our study. HULC expression in GC tissue and GC cell lines (MKN45, SGC-7901, MKN28, AGS) was detected by qRT-PCR. Cell viability, colony formation, migration, invasion and cell apoptosis were examined by CCK-8 assay, survival fraction assay, modified two-chamber migration assay, Millicell Hanging Cell Culture and flow cytometry analysis, respectively. The expression of matrix metalloproteinase (MMP)-2/9 and vimentin was detected by qRT-PCR and western blot, respectively. The expression of PI3K/AKT and JNK was measured by western blot. The expression of HULC was up-regulated both in GC tissue and cell lines (P < .05, P < .01 or P < .001). GEN negatively regulated the expression of HULC in MKN45 cells (P < .05 or P < .01). GEN decreased cell viability (P < .05), colony formation (P < .01), migration (P < .05) and invasion (P < .05) while HULC overexpression led to the opposite results in GEN-treated cells. The expression of phosphatidylinositol 3' -kinase (PI3K)/ protein kinase B (AKT) and c-Jun N-terminal kinase (JNK) was down-regulated by GEN (all P < .05) while reversed by HULC overexpression. HULC was up-regulated in GC. GEN inhibited MNK45 cell viability, colony formation, migration and invasion while induced cell apoptosis by down-regulation of HULC in MKN45 cells. GEN inactivated PI3K/AKT and JNK signal pathways through down-regulation of HULC.
胃癌（GC）是一种发病率和死亡率都很高的严重疾病。栀子苷（GEN）具有多种生物学特性，包括抗肿瘤功能。然而，GEN 对 GC 的作用尚未得到很好的研究。因此，本研究探讨了 GEN 对 GC 的影响。通过 qRT-PCR 检测 GC 组织和 GC 细胞系（MKN45、SGC-7901、MKN28、AGS）中的 HULC 表达。通过 CCK-8 测定、存活分数测定、改良双层迁移测定、Millicell 悬挂细胞培养和流式细胞术分析分别检测细胞活力、集落形成、迁移、侵袭和细胞凋亡。通过 qRT-PCR 和 Western blot 分别检测基质金属蛋白酶（MMP）-2/9 和波形蛋白的表达。通过 Western blot 测定 PI3K/AKT 和 JNK 的表达。GC 组织和细胞系中 HULC 的表达均上调（P<0.05，P<0.01 或 P<0.001）。GEN 下调 MKN45 细胞中 HULC 的表达（P<0.05 或 P<0.01）。GEN 降低细胞活力（P<0.05）、集落形成（P<0.01）、迁移（P<0.05）和侵袭（P<0.05），而 HULC 过表达导致 GEN 处理细胞的相反结果。GEN 下调磷脂酰肌醇 3' -激酶（PI3K）/蛋白激酶 B（AKT）和 c-Jun N-末端激酶（JNK）的表达（均 P<0.05），而过表达 HULC 则逆转了这一结果。HULC 在 GC 中上调。GEN 通过下调 MKN45 细胞中的 HULC 抑制 MKN45 细胞活力、集落形成、迁移和侵袭，同时诱导细胞凋亡。GEN 通过下调 HULC 使 PI3K/AKT 和 JNK 信号通路失活。
