Asiaticoside Inhibits Epithelial-mesenchymal Transition and Stem Cell-like Properties of Pancreatic Cancer PANC-1 Cells by Blocking the Activation of P65 and P38MAPK

Overview

Journal J Gastrointest Oncol

Date 2021 Mar 12

PMID 33708436

Citations 5

Authors

Yonggang He

Xuehui Peng

Lu Zheng

Yichen Tang

Jing Li

Xiaobing Huang

Affiliations

Soon will be listed here.

Abstract

Background: To analyze the inhibitory effects of Asiaticoside (ATS) on the epithelial-mesenchymal transition (EMT) and stem cell-like properties of a pancreatic cancer cell line (PANC-1) by blocking the activation of p65 and p38 mitogen-activated protein kinase (p38MAPK).

Methods: ATS concentrations were set at 0, 10, 25, and 50 µmol/L. The survival rate of PANC-1 cells in each group was detected by CCK-8, and CD133 and CD44 positive cells were detected by flow cytometry. The levels of Ki67 and proliferating cell nuclear antigen (PCNA) mRNA were detected by RT-PCR. The expression of E-cadherin, N-cadherin, vimentin, sex-determining region Y-box2 (SOX2), and octamer-binding transcription factor 4 (OCT4) proteins, and the phosphorylation levels of p65 and p38MAPK were detected by western blot. Nude mouse xenograft models of the tumor were established by subcutaneous injection of PANC-1 cells (1×10-1×10/mL), and they were randomly divided into the control group (0 mg/kg), and low-dose, medium-dose, and high-dose ATS groups (2.5, 5, 10 mg/kg). Apoptosis in xenograft tissue was detected by TUNEL, and the expression of vimentin and SOX2 proteins was detected by immunohistochemistry.

Results: As the ATS concentration increased to 25 µmol/L, cell survival rate, levels of Ki67 and PCNA mRNA, expression of N-cadherin, vimentin, SOX2, OCT4, p-p65/p65, and p-p38MAPK/p38MAPK proteins, and the proportions of CD44 and CD133 positive cells significantly decreased (P<0.05), while the expression of E-cadherin protein significantly increased (P<0.05). The results of tumor formation in nude mice showed that with the increase of ATS concentration, at 5 mg/kg the volume of the xenograft significantly decreased (P<0.05), the apoptosis rate significantly increased (P<0.05), and positive expression rates of vimentin and SOX2 proteins significantly decreased (P<0.05).

Conclusions: ATS may inhibit the proliferation, EMT, and stem cell-like properties of pancreatic cancer cells by blocking the phosphorylation of p38MAPK and nuclear factor-κB (NF-κB)/p65 in PANC-1 cells.

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