Matrine reduces the proliferation of A549 cells via the p53/p21/PCNA/eIF4E signaling pathway

Abstract

The aim of the present study was to investigate how matrine affects the proliferation of A549 human lung adenocarcinoma cells via the p53/p21/proliferating cell nuclear antigen (PCNA)/eukaryotic translation initiation factor 4E (eIF4E) signaling pathway. The effect of different concentrations of matrine on the proliferation of A549 cells was investigated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The migration of A549 cells following exposure to varied concentrations of matrine was detected using a Transwell cell migration assay. The effect of 240 mg/l matrine on the apoptotic rate of A549 cells was determined using flow cytometry. The change in the mRNA and protein expression levels of p53, p21, PCNA and eIF4E following exposure to matrine were detected using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. The increase of matrine from 60–240 mg/l led to reduced cell migration and inhibition of A549 cell proliferation. The apoptotic rate of A549 cells when treated with 240 mg/l matrine was significantly different when compared with the untreated control. The mRNA expression levels of p53 and p21 in the group treated with 240 mg/l matrine were significantly higher compared with the control group. The mRNA expression levels of PCNA and eIF4E were significantly lower in the 240 mg/l matrine-treated group compared with the control. The protein expression levels of p53 and p21 were significantly higher in the 240 mg/l matrine group compared with the control group. Treatment with 240 mg/l matrine reduced the protein expression levels of PCNA and eIF4E. Matrine also reduced the migration ability of A549 cells and inhibited their proliferation, which may be associated with the overexpression of p53 and p21, and the reduction of PCNA and eIF4E expression levels.

Matrine inhibits TPC‑1 human thyroid cancer cells via the miR‑21/PTEN/Akt pathway

“…Furthermore, matrine induced apoptosis and cell cycle arrest in TPC-1 cells. These results were consistent with those previously obtained in studies investigating other cancers ( 14 , 15 , 17 ,14).…”

“…In addition to the PTEN/Akt signaling, miR-21 serves important roles in cancer growth, proliferation, migration and metastasis by targeting programmed cell death 4 and Sprouty RTK signaling antagonist 1, or by upregulating Bcl-2 indirectly ( 10 , 13 , 31 ). Overexpression of PTEN upregulates the p21/WAF1/CIP1 and p27/KIP1 pathways by dephosphorylating Akt to increase cell apoptosis and/or induce G1 phase arrest ( 17 , 23 ). These issues should be further investigated in thyroid cancer cells.…”

A novel multi-scale bioinformatics strategy for identifying the molecular mechanism by insighting into ceRNA network integrating WGCNA and meta-analysis: compound kushen injection for treating gastric carcinoma as a proof

“…Analysis of miRNA's KEGG pathway demonstrated that most of the target genes are enriched in Hippo signaling pathway and p53 signaling pathway, which are closely related to the proliferation and metastasis of cancer cells. Matrine plays an important role in regulating p53 signaling pathway to inhibit cell proliferation in liver cancer, lung cancer and esophageal cancer [80][81][82]. Besides, matrine can also promote colorectal cancer cell apoptosis via Hippo signaling pathway [83].…”

Autophagy inhibition enhances Matrine derivative MASM induced apoptosis in cancer cells via a mechanism involving reactive oxygen species-mediated PI3K/Akt/mTOR and Erk/p38 signaling

“…Several studies have investigated the anticancer activity of matrine. Lu et al had reported an induction of ~ 25% apoptosis in A549 after 48 h exposure to matrine [47], and Wang et el., have shown that long-term (48 h) exposure of matrine at high doses (2000 μg/ml) can induce moderate (15%) apoptosis in cisplatin-resistance A549 [48]. Other studies have shown that matrine at a dose of 100 μg/ml matrine for 48 h can diminish proliferation of cervical cancer cells by reducing the expression of matrix metalloproteinases through suppression of p38 signaling pathway [49].…”