Isoliquiritigenin inhibits proliferation and metastasis of MKN28 gastric cancer cells by suppressing the PI3K/AKT/mTOR signaling pathway

Abstract

Isoliquiritigenin (ISL) is a flavonoid extracted from licorice root, which is known to serve important antitumor roles in numerous types of cancers; however, its effect on gastric cancer remains to be elucidated. The present study aimed to explore the roles and underlying mechanisms of ISL in MKN28 gastric cancer cells. MKN28 cell proliferation was measured using the Cell Counting Kit‑8 (CCK8) assay. A Transwell assay was used to determine the effects of ISL on the migration and invasion of MKN28 cells. Apoptosis was assessed by flow cytometry, and the expression levels of apoptosis‑, autophagy‑ and signaling pathway‑related proteins were detected by western blot analysis. The results of the CCK8 assay demonstrated that ISL significantly inhibited the proliferation of MKN28 cells (P<0.05). Transwell assays demonstrated that the migration and invasion of MKN28 cells were significantly inhibited following treatment with ISL (P<0.05). Flow cytometric analysis indicated that ISL induced apoptosis of MKN28 cells. In addition, western blot analysis revealed that the ratio of microtubule‑associated proteins 1A/1B light chain 3B (LC3)II/LC3I was upregulated, as was Beclin 1 expression; however, p62 was downregulated following ISL pretreatment, thus suggesting that ISL triggered autophagy in MKN28 cells. In addition, the phosphorylation levels of protein kinase B (AKT) and mammalian target of rapamycin (mTOR) were significantly reduced following ISL treatment. These results indicated that ISL may influence apoptosis and autophagy in MKN28 cells by suppressing the phosphoinositide 3‑kinase/AKT/mTOR signaling pathway. In conclusion, the findings of the present study suggested that ISL may inhibit MKN28 cell proliferation, migration and invasion by inducing apoptosis and autophagy, implying potential as a therapeutic agent for gastric cancer.

Mechanisms underlying isoliquiritigenin‐induced apoptosis and cell cycle arrest via ROS‐mediated MAPK/STAT3/NF‐κB pathways in human hepatocellular carcinoma cells

“…Furthermore, the STAT3 signaling pathway plays a key role in regulating the cell cycle and apoptosis. It has been suggested that the expression of downstream cell cycle and proapoptotic genes is reduced when the JAK/STAT3 signaling pathway is blocked (Zhang, Feng, et al, ; Zhang, Lu, et al, ; Zhang, Wang, et al, ). In our study, ISL promoted cell cycle arrest at the G2/M phase in HepG2 cells by inhibiting the activation of STAT3 (Figure a).…”

“…Excessive ROS leads to an imbalance in oxidative stress and the cellular redox state, and promotes cell apoptosis and necrosis under many physiological or pathological conditions (Zhang, Feng, et al, ; Zhang, Lu, et al, ; Zhang, Wang, et al, ). It has been reported that ISL contains an Michael electrophilic pharmacophore (α,β‐unsaturated carbonyl), which can be used as a tool to regulate the oxidative stress (Amslinger, ).…”

“…Isoliquiritigenin (ISL) is the main biologically active component of Glycyrrhiza and has many pharmacological properties such as anti‐inflammatory, antiviral, and anticancer effects (Lin, Sun, Dang, & Li, ; Peng et al, ). It also exhibits inhibitory effects on various tumor cells by inhibiting proliferation, inducing apoptosis, or causing cell cycle arrest (Chen et al, ; Xiang et al, ; Zhang, Wang, Sun, & Wei, ). However, the antitumor effects of ISL on HCC remain unknown.…”

VGLL3 is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in stomach adenocarcinoma

“…Therefore, we next analyzed the pathways enriched in genes that strongly correlated with VGLL3 expression (r > 0.7), and identified the PI3K/Akt/mTOR signaling pathway, ECM receptor interaction, and focal adhesion pathway. The PI3K/AKT/mTOR signaling pathway plays a significant role in tumor cell proliferation, growth and survival, in addition to modulating the tumor microenvironment and tumor-associated macrophages (TAMs) [41][42][43][44][45][46][47] . ECM and focal adhesion molecules, including PLXDC2, PDGFRB, FSTL1, TIMP2, FAP, SPARC, AEBP1, NOX4, and FBLN2 are known to regulate macrophage mobilization into tumor tissues 19,20,[48][49][50] , and are associated with TAM 51-53 .…”

Tissue Mechanics and Expression of TROP2 in Oral Squamous Cell Carcinoma with Varying Differentiation

“…PTEN is a well-known tumor suppressor that is a phosphatase [36] and affects the PI3K/PKB/AKT channel during the dephosphorylation of PIP-2 and PIP-3 [37]. PI3K signaling is important in regulating tumor cell proliferation, migration, and invasion [38,39]. Thus, PTEN is a negative regulator of cancer [40,41].…”