Aloin inhibits gastric cancer cell proliferation and migration by suppressing the STAT3/HMGB1 signaling pathway.
10.12122/j.issn.1673-4254.2023.05.04
- Author:
Fei GE
1
;
Mengqi WAN
1
;
Zhenyu CHENG
1
;
Xuelei CHEN
1
;
Qianyi CHEN
1
;
Zhilin QI
1
Author Information
1. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Wannan Medical College, Wuhu 241002, China.
- Publication Type:Journal Article
- Keywords:
aloin;
gastric cancer;
high mobility group box protein 1;
migration;
proliferation
- MeSH:
Humans;
Animals;
Mice;
Stomach Neoplasms;
Cyclin B1;
Matrix Metalloproteinase 2;
Matrix Metalloproteinase 9;
HMGB1 Protein;
Signal Transduction;
Cell Proliferation;
STAT3 Transcription Factor
- From:
Journal of Southern Medical University
2023;43(5):702-709
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the molecular mechanism underlying the inhibitory effect of aloin on the proliferation and migration of gastric cancer cells.
METHODS:Human gastric cancer MGC-803 cells treated with 100, 200 and 300 μg/mL aloin were examined for changes in cell viability, proliferation and migration abilities using CCK-8, EdU and Transwell assays. HMGB1 mRNA level in the cells was detected with RT-qPCR, and the protein expressions of HMGB1, cyclin B1, cyclin E1, E-cadherin, MMP-2, MMP-9 and p-STAT3 were determined using Western blotting. JASPAR database was used to predict the binding of STAT3 to HMGB1 promoter. In a BALB/c-Nu mouse model bearing subcutaneous MGC-803 cell xenograft, the effect of intraperitoneal injection of aloin (50 mg/kg) on tumor growth was observed. The protein expressions of HMGB1, cyclin B1, cyclin E1, E-cadherin, MMP-2, MMP-9 and p-STAT3 in the tumor tissue was examined using Western blotting, and tumor metastasis in the liver and lung tissues was detected using HE staining.
RESULTS:Treatment with aloin concentration-dependently inhibited the viability of MGC-803 cells (P < 0.05), significantly reduced the number of EdU-positive cells (P < 0.01), and attenuated the migration ability of the cells (P < 0.01). Aloin treatment dose-dependently down-regulated HMGB1 mRNA expression (P < 0.01), lowered the protein expressions of HMGB1, cyclin B1, cyclin E1, MMP-2, MMP-9 and p-STAT3, and up-regulated E-cadherin expression in MGC-803 cells. Prediction based on JASPAR database suggested that STAT3 could bind to the promoter region of HMGB1. In the tumor-bearing mice, aloin treatment significantly reduced the tumor size and weight (P < 0.01), lowered the protein expressions of cyclin B1, cyclin E1, MMP-2, MMP-9, HMGB1 and p-STAT3 and increased the expression of E-cadherin in the tumor tissue (P < 0.01).
CONCLUSION:Aloin attenuates the proliferation and migration of gastric cancer cells by inhibiting the STAT3/HMGB1 signaling pathway.
