<p>Ropivacaine Inhibits the Growth, Migration and Invasion of Gastric Cancer Through Attenuation of WEE1 and PI3K/AKT Signaling via miR-520a-3p</p>

Abstract

Background: Metastasis remains one of the greatest challenges involved in treating gastric cancer (GC). Ropivacaine (Rop) is not only a well-documented local anesthetic medicament but also has been reported to exert an antitumor role in cancer development. This study explored the effects of ropivacaine on the growth, migration and invasion of gastric cancer and the underlying mechanisms. Methods: Cell Counting Kit-8 (CCK8) assay was conducted to test the effect of Rop on the proliferation of AGS and BGC-823 GC cells. Moreover, cell apoptosis, migration and invasion were examined by flow cytometry and transwell assay, respectively. The expression of miR-520a-3p was determined by qRT-PCR. miRNA targeting sites were analyzed using bioinformatics analysis and dual-luciferase reporter assay. Protein levels of WEE1 and PI3K/ AKT were detected by Western blot. Furthermore, the tumor-forming experiment of nude mice was used to detect the growth of cells in vivo. Results: Rop inhibited proliferation but promoted apoptosis of GC cells. Besides, the migration and invasion of GC cells were also inhibited by Rop. Moreover, miR-520a-3p expression was enhanced by Rop, and transfection with miR-520a-3p mimic decreased cell proliferation, migration and invasion. The upregulation of miR-520a-3p was partly contributed to the inhibitory effect of ropivacaine on GC cell lines. Finally, Rop inactivated WEE1 and PI3K/AKT pathway via upregulation of miR-520a-3p. Conclusion: Our results suggested that Rop decreased growth, migration and invasion of GC cells via regulating miR-520a-3p expression and further inactivated WEE1 and PI3K/ AKT signaling pathways.

<p>USP8 Inhibitor Suppresses HER-2 Positive Gastric Cancer Cell Proliferation and Metastasis via the PI3K/AKT Signaling Pathway</p>

“…In previous studies, the PI3K/AKT pathway was reported as a major signaling pathway associated with tumor progression and invasion. 31,32 Therefore, we then examined the expression of PI3K/AKT-signaling-related molecules. The expression of p-AKT, and p-PI3K was lower in NCI-N87 with USP8 inhibitor group in Figure 5B.…”

Ropivacaine Inhibits Wound Healing by Suppressing the Proliferation and Migration of Keratinocytes via the PI3K/Akt/mTOR Pathway

“…There have been many studies inhibition of PI3K/AKT signaling pathway of ropivacaine in vivo and in vitro [15][16][17]. Meanwhile, activation of the PI3K/Akt/mTOR signaling pathway has been con rmed to be closely related to the proliferation and migration of human keratinocytes [18][19][20].…”

“…PI3K/Akt/mTOR pathway plays a crucial role in the proliferation, migration, metabolism and apoptosis of various cells [12][13][14]. Recent experimental studies have shown that ropivacaine decreased growth, migration and invasion of gastric cancer cells by inactivating the PI3K/Akt/mTOR signaling pathway [15].…”

MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers

“…For example, miR-340, miR-379, miR-520a-3p, and miR-1254 inhibit the PI3K/AKT/mTOR signaling pathway by suppressing the direct targets SPP1, FAK, WEE1, and SMURF1. It is reported that an increase in the expression levels of miR-379, 520a-3p, 1254, and miR-340 resulted in a decrease in AKT phosphorylation [67][68][69][70] The other microRNAs directly interact with the main components of the PI3K/AKT/mTOR pathway. PI3K is acted upon by miR-142-5p, miR-216, and miR-491, inhibiting this pathway.…”