Introduction: Platycodin D (PD), a triterpenoid saponin isolated from Platycodon grandiflorum, has a well-known anti-tumor effect in multiple human cancers, including gastric cancer (GC). miR-34a plays an important role in the progression of GC. However, the relationship between miR-34a and the susceptibility of GC cells to PD is still unclear. The aim of our research was to investigate the functions of miR-34a in mediating the susceptibility of GC to PD. Methods: qPCR was performed to detect the expression level of miR-34a and survivin in GC cells. The expression of survivin, Bcl-2, Bax, and cleaved caspase-3 was analyzed using Western blot. Cell viability was detected by MTT assay, and apoptosis was analyzed via Annexin V-FITC/PI staining followed by flow cytometry. The colony formation and scratch-wound assays were applied to assess cell proliferation and migration. Caspase-3/7 activity was detected by a Caspase-Glo®3/7 detection kit. The relationship between miR-34a and survivin was determined by dual luciferase reporter gene assay. Finally, a GC xenograft mouse model was used to confirm our findings in vivo. Results: The expression of miR-34a decreased but survivin increased inversely in human GC cells. Survivin is a direct target of miR-34a and may be negatively regulated by miR-34a. PD could inhibit GC cell proliferation and induce apoptosis. Importantly, overexpression miR-34a or suppressing survivin was shown to enhance the susceptibility of GC to PD both in vitro and in vivo. Conclusions: miR-34a could modulate the susceptibility of GC to PD via targeting survivin, suggesting miR-34a overexpression may serve as a novel strategy to sensitize GC to anti-cancer drugs.

中文翻译：

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miR-34a 通过靶向 Survivin 增强胃癌对桔梗素 D 的易感性

简介：桔梗素 D (PD) 是一种从桔梗中分离出来的三萜皂苷，在包括胃癌 (GC) 在内的多种人类癌症中具有众所周知的抗肿瘤作用。miR-34a 在 GC 的进展中起重要作用。然而，miR-34a与GC细胞PD易感性之间的关系仍不清楚。我们研究的目的是研究 miR-34a 在介导 GC 对 PD 易感性中的功能。方法：采用qPCR检测胃癌细胞中miR-34a和survivin的表达水平。使用蛋白质印迹分析存活蛋白、Bcl-2、Bax 和裂解的 caspase-3 的表达。MTT法检测细胞活力，Annexin V-FITC/PI染色后流式细胞术分析细胞凋亡。集落形成和划痕试验用于评估细胞增殖和迁移。Caspase-3/7 活性通过 Caspase-Glo®3/7 检测试剂盒检测。通过双荧光素酶报告基因测定确定miR-34a和存活蛋白之间的关系。最后，使用 GC 异种移植小鼠模型来证实我们的体内发现。结果：在人胃癌细胞中，miR-34a的表达降低，而survivin的表达呈相反的增加。Survivin 是 miR-34a 的直接靶标，可能受到 miR-34a 的负调控。PD可以抑制GC细胞增殖并诱导细胞凋亡。重要的是，在体外和体内，过表达 miR-34a 或抑制 survivin 被证明可以增强 GC 对 PD 的易感性。结论：miR-34a可通过靶向survivin调节GC对PD的易感性，