title: Upregulation of miR-34a by diallyl disulfide suppresses invasion and induces apoptosis in SGC-7901 cells through inhibition of the PI3K/Akt signaling pathway.
abstract: Diallyl disulfide (DADS) exerts anticarcinogenic activity in various types of cancer. However, the mechanism underlying its anticarcinogenic activity remains to be elucidated. The aim of the present study was to explore the mechanism of the anticarcinogenic activity of DADS in gastric cancer (GC). The expression levels of microRNA (miR)-34a in GC and normal tissues were measured using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of miR-34a was also measured using RT-qPCR in SGC-7901 cells following treatment with DADS. In addition, the effect of DADS on the invasion capability of SGC-7901 cells was observed in the presence of miR-34a or anti-miR-34a using a Matrigel invasion assay. Furthermore, in identical conditions, the apoptosis of SGC-7901 cells was observed using flow cytometry. Finally, the present study investigated the effects of DADS and miR-34a on the phosphoinositide 3-kinase (PI3K)/Akt signaling pathwayin vitro. The level of miR-34a in GC tissues was reduced compared with that in adjacent normal tissues (P<0.05). Treatment with DADS upregulated miR-34a expression in SGC-7901 cells (P<0.05). In the Matrigel invasion assay, DADS inhibited the invasive capability of SGC-7901 cells (P<0.05 vs. control), which was improved by overexpression of miR-34a (P<0.01 vs. control) but reduced by downregulation of miR-34a (P<0.05 vs. DADS treatment group). Furthermore, DADS induced apoptosis of SGC-7901 cells (P<0.05 vs. control); and DADS and miR-34a synergistically enhanced apoptosis of SGC-7901 cells (P<0.01 vs. control). In addition, DADS and miR-34a inhibited the expression levels of phosphorylated (p)-PI3K and p-Akt (P<0.05 vs. control). By contrast, downregulation of miR-34a alleviated the decrease in p-PI3K and p-Akt expression induced by DADS (P<0.05 vs. DADS treatment group). Cell viability was reduced with increasing concentrations of DADS, however, DADS did not affect cell viability following inhibition of the PI3K/Akt signaling pathway. In conclusion, DADS suppresses invasion and induces apoptosis of SGC-7901 cells by upregulation of miR-34a, via inhibition of the PI3K-Akt signaling pathway.
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Xiefu
authors.initials: X
authors.lastname: Zhang
keywords: apoptosis; diallyl disulfide; gastric cancer; invasion; microRNA-34a; phosphoinositide 3-kinase/Akt signaling pathway