Fentanyl inhibits the progression of gastric cancer through the suppression of MMP-9 via the PI3K/Akt signaling pathway

被引:22
|
作者
Li, Chunlai [1 ]
Qin, Yi [1 ]
Zhong, Yu [1 ]
Qin, Yinying [1 ]
Wei, Yi [1 ]
Li, Li [1 ]
Xie, Yubo [1 ]
机构
[1] Guangxi Med Univ, Dept Anesthesiol, Affiliated Hosp 1, 6 Shuang Yong Rd, Nanning 530021, Guangxi, Peoples R China
关键词
Fentanyl; stomach neoplasm; cell proliferation; apoptosis; matrix metalloproteinase-9 (MMP-9); MGC-803; CELLS; TUMOR-GROWTH; MIGRATION; INVASION; MORPHINE; METASTASIS; CYCLE;
D O I
10.21037/atm.2019.12.161
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Fentanyl is a drug commonly used for perioperative and postoperative analgesia. Previous studies have confirmed that fentanyl can affect the progression of gastric cancer; however, this effect has not yet been elucidated. The purpose of our study was thus to investigate the role of fentanyl in gastric cancer and clarify its potential mechanisms. Methods: A CCK-8 assay was used to determine the proliferation of MGC-803 cells, while Transwell assay and wound healing assay were used to determine the invasion and migration abilities, respectively. Apoptosis and the cell cycle were assessed by flow cytometry, and the ultrastructure of the cells was examined with a transmission electron microscope. The mRNA expression levels of serine-threonine protein kinase 1 (Akt-1), matrix metalloproteinase-9 (NIMP-9), and death-associated protein kinase 1 (DAPK1) were evaluated by real-time (RT) quantitative PCR. The protein expression of p-Akt, MMP-9, and caspase-9 was detected by western blot analysis. To study the interaction of fentanyl with the phosphatidylinositol-3-kinase (PI3K)/Akt/MMP-9 pathway, PI3K inhibitor (LY294002) and MMP-9 inhibitor (SB-3CT) were used to treat the MGC-803 cells. Results: Findings indicated that fentanyl inhibits the proliferation, invasion, and migration of MGC-803 cells. Specifically, fentanyl inhibits the expression of MMP-9 and enhances the expression of apoptosis-promoting factors such as caspase-9 and DAPK1 through the PI3K/Akt signaling pathway. Cell cycle arrest was observed in the G0/G1 phase. Furthermore, the inhibition of PI3K/Akt/MMP-9 by LY294002 and SB-3CT enhanced the anticancer effects of fentanyl. Conclusions: Fentanyl inhibits the proliferation, invasion and migration of gastric cancer cells by inhibiting the PI3K/Akt/MMP-9 pathway, which could be very useful for gastric cancer treatment.
引用
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页数:10
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