Dextran sulfate inhibits proliferation and metastasis of human gastric cancer cells via miR-34c-5p

Abstract

Background: Gastric cancer (GC) is a malignant tumor with a high global mortality rate that is currently difficult to treat. Dextran sulfate (DS), a safe anti-tumor agent, can effectively inhibit the malignant biological behavior of gastric cancer; however, its mechanism of action is not fully understood. Therefore, this study aimed at elucidate the potential mechanisms of action. Methods: In this study we used DS to intervene in lentivirus-transfected gastric cancer cells to observe the effect of DS on miR-34c-5p. RT-qPCR, CCK-8, clone formation assay, wound healing assay, transwell assay and western blot were used to examine whether DS affects the proliferation and metastasis of gastric cancer cells via miR-34c-5p. The results were validated using in vivo experiments. Results: Our data confirmed that DS up-regulated miR-34c-5p expression in human gastric cancer cells. Moreover, DS intervention enhanced the inhibitory effect of miR-34c-5p over-expression on the proliferation, invasion, and migration of gastric cancer cells, and partially reversed the promotive effect of miR-34c-5p on the proliferation, invasion, and migration of gastric cancer cells. In addition, DS could affect the activation of the MAP2K1/ERK signaling pathway through the up-regulation of miR-34c-5p, thereby inhibiting the malignant biological behavior of gastric cancer. Finally, it was demonstrated that DS could also inhibit the expression of MAP2K1 in vivo, which in turn inhibits the activation of the ERK signaling pathway to exert anti-cancer effects. Conclusion: DS may inhibit the proliferation and metastasis of gastric cancer cells by regulating miR-34c-5p, which may be a new option for clinical treatment.

Keywords

• Dextran sulfate
• Gastric cancer
• miR-34c-5p
• Proliferation
• Metastasis