<p>Aloin Inhibits the Proliferation and Migration of Gastric Cancer Cells by Regulating NOX2–ROS-Mediated Pro-Survival Signal Pathways</p>

Abstract

Background: Aloin has been reported to have many pharmacological effects including antiinflammatory, anti-oxidant and anti-tumour activities. However, the precise molecular mechanisms underlying the anti-tumour properties of aloin are yet to be elucidated. Methods: HGC-27 and BGC-823 gastric cancer cells were treated with aloin. EdU and colony formation assays were used to detect the proliferation ability of cells. The migration of cells was detected using wound healing and transwell assays. Western blotting was used to detect the levels of cyclinD1, cyclin E1, MMPs, N-cadherin, E-cadherin and NOX2. The phosphorylation of Akt, mTOR, P70S6K, S6, Src, stat3 and IκBα were also detected by Western blotting. Flow cytometry was used to detect the cell cycle distribution.The location of p65 in cells was determined by using a confocal microscopy assay. The total amounts of ROS present in cells were measured using an ROS assay kit. Results: Here, we found that aloin inhibited the proliferation and migration of HGC-27 and BGC-823 gastric cancer cells using a combination of EdU, colony formation, wound healing and transwell assays. Further investigations revealed that aloin decreased the protein expression levels of cyclin D1, N-cadherin, and the matrix metalloproteinases (MMP)-2 and MMP-9; increased E-cadherin expression in a dose-dependent manner; inhibited reactive oxygen species (ROS) generation; and mediated the activation of Akt-mTOR, signal transducer and activator of transcription-3 (Stat3), and NF-κB signalling pathways. Our results also indicated that aloin is able to attenuate the expression levels of the two regulatory proteins of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), p47 phox and p22 phox , but had no effect on the level of gp91 phox. N-acetylcysteine treatment of gastric cancer cells inhibited ROS production and Akt-mTOR, Stat3, and IκBα phosphorylation. Taken together, our data suggest that aloin inhibits the proliferation and migration of gastric cancer cells by downregulating NOX2-ROS-mediated activation of the Akt-mTOR, Stat3, and NF-κB signalling pathways. Conclusion: Our findings suggest a potential role for aloin in the prevention of gastric cancer cell proliferation and migration and provide novel insights into the anti-cancer properties of aloin.

High mobility group box 1 regulates gastric cancer cell proliferation and migration via RAGE-mTOR/ERK feedback loop

“…Western blotting was performed according to the methods described previously by Wang et al 15 . Total protein was extracted from cells using radioimmunoprecipitation assay buffer (Beyotime Institute of Biotechnology, Haimen, China) supplemented with phenylmethylsulfonyl fluoride (PMSF).…”

Up-regulation of DGAT1 in cancer tissues and tumor-infiltrating macrophages influenced survival of patients with gastric cancer

“…Surprisingly, A922500 treatment also inhibited expression of NOX2 and indoleamine 2,3-dioxygenase (IDO) in MKN45 (Fig. 4 d, e), two genes correlated with proliferation and migration of gastric tumor cells [ 15 , 16 ]. Collectively, oleate sodium elevated DGAT1 expression in gastric cancer cell line MKN45 and DGAT1 blockade induced cell apoptosis in vitro.…”

“…Data from several studies suggest that suppressed DGAT1 is a promising strategy to inhibit prostate cancer cell growth and, therefore, targeting DGAT1 might be conducive for clinical gastric cancer treatment [ 12 , 13 ]. It has been previously reported that the elevated level of reactive oxygen species is facilitated to cancer progression and metastasis, and gastric cancer cell proliferation and migration could be suppressed after administration of inhibitor to block the reactive oxygen species production [ 14 – 16 ]. Another study demonstrated that accumulation of the nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) activates Akt, Stat3, and IκBα signaling pathways in two gastric cancer cells.…”

“…Another study demonstrated that accumulation of the nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) activates Akt, Stat3, and IκBα signaling pathways in two gastric cancer cells. Restrained NOX2 expression decreases cyclin D1 expression and leads to cell growth arrest [ 16 ]. However, much uncertainty still exists about the relationship between DGAT1 and the reactive oxygen species in gastric cancer progression.…”

Dexmedetomidine Attenuates LPS-Induced Monocyte-Endothelial Adherence via Inhibiting Cx43/PKC-α/NOX2/ROS Signaling Pathway in Monocytes

“…NADPH oxidases contain different subtypes, which are well known to be involved in signal transduction associated with inflammation and oxidative stress [27,28]. In these subtypes, NOX2 abundantly expressing in monocytes is currently accepted as the main source of ROS [29,30]. PKC activation also has been identified to play an important part in inflammation and oxidative stress [31,32].…”