二烯丙基二硫化物上调miR-34a通过抑制PI3K/Akt信号通路抑制SGC-7901细胞的侵袭并诱导其凋亡。
Upregulation of miR-34a by diallyl disulfide suppresses invasion and induces apoptosis in SGC-7901 cells through inhibition of the PI3K/Akt signaling pathway.
作者信息
Wang Guojun, Liu Guanghui, Ye Yanwei, Fu Yang, Zhang Xiefu
机构信息
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
出版信息
Oncol Lett. 2016 Apr;11(4):2661-2667. doi: 10.3892/ol.2016.4266. Epub 2016 Feb 24.
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 pathway . 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.
二烯丙基二硫化物（DADS）在多种癌症中发挥抗癌活性。然而，其抗癌活性的潜在机制仍有待阐明。本研究的目的是探讨DADS在胃癌（GC）中抗癌活性的机制。采用逆转录定量聚合酶链反应（RT-qPCR）检测GC组织和正常组织中微小RNA（miR）-34a的表达水平。在用DADS处理后的SGC-7901细胞中，也使用RT-qPCR检测miR-34a的表达。此外，使用基质胶侵袭试验在存在miR-34a或抗miR-34a的情况下观察DADS对SGC-7901细胞侵袭能力的影响。此外，在相同条件下，使用流式细胞术观察SGC-7901细胞的凋亡情况。最后，本研究调查了DADS和miR-34a对磷酸肌醇3激酶（PI3K）/Akt信号通路的影响。与相邻正常组织相比，GC组织中miR-34a的水平降低（P<0.05）。用DADS处理可上调SGC-7901细胞中miR-34a的表达（P<0.05）。在基质胶侵袭试验中，DADS抑制了SGC-7901细胞（与对照组相比，P<0.05）的侵袭能力，miR-34a过表达可增强这种抑制作用（与对照组相比，P<0.01），而miR-34a下调则降低了这种抑制作用（与DADS处理组相比，P<0.05）。此外，DADS诱导SGC-7901细胞凋亡（与对照组相比，P<0.05）；DADS和miR-34a协同增强SGC-7901细胞的凋亡（与对照组相比, P<0.01）。此外，DADS和miR-34a抑制磷酸化（p）-PI3K和p-Akt的表达水平（与对照组相比，P<0.05）。相比之下，miR-34a下调减轻了DADS诱导的p-PI3K和p-Akt表达的降低（与DADS处理组相比，P<0.05）。随着DADS浓度的增加，细胞活力降低，然而，抑制PI3K/Akt信号通路后，DADS不影响细胞活力。总之，DADS通过上调miR-34a抑制PI3K-Akt信号通路，从而抑制SGC-7901细胞的侵袭并诱导其凋亡。
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