miR-34a Enhances the Susceptibility of Gastric Cancer to Platycodin D by Targeting Survivin.

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 cy-tometry. 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.