Parthenolide Induces Gallbladder Cancer Cell Apoptosis Via MAPK Signalling

Overview

Journal Ann Med Surg (Lond)

Publisher Wolters Kluwer

Specialty Medical Education

Date 2024 Apr 5

PMID 38576937

Authors

Halmurat Obulkasim

Gulibositan Aji

Abudoukaher Abudoula

Yu Liu

Shaobin Duan

Affiliations

Soon will be listed here.

Abstract

Objective: Parthenolide (PTL) has a wide range of clinical applications owing to its anti-inflammatory and antitumor effects. To date, the antitumor effect of PTL on gallbladder cancer (GBC) remains largely unknown. Therefore, we aimed to investigate the biological effects of PTL on GBC.

Methods: The cellular viability and proliferation of GBC-SD and NOZ cell lines after treatment with different concentrations of PTL were analyzed using the Cell Counting Kit-8 (CCK8)assay and colony formation assay. Apoptosis analysis was performed using flow cytometry. Hoechst staining was performed. RNA sequencing (RNA-seq) was performed to identify PTL-related genes and signalling pathways. Furthermore, we confirmed the involvement of these signalling pathways by qRT-PCR and western blotting. For the in-vivo experiments, a xenograft model was used to evaluate the effects of PTL on the proliferation of NOZ cells.

Results: PTL significantly inhibited GBC cell growth and induced apoptosis in the GBC-SD and NOZ cell lines in a dose-dependent manner. RNA sequencing data showed that the immune response and mitogen-activated protein kinase (MAPK) signalling pathways are closely associated with PTL-induced gallbladder cancer cell apoptosis. PTL upregulated BAX, cleaved PARP-1, cleaved caspase-3, cleaved caspase-9, P53 and decreased the expression of BCL-2, phosphorylated ERK, and phosphorylated MEK . Tumour volume and weight were also suppressed by PTL . Moreover, the effects of PTL on GBC cells might be mediated by the MAPK pathway.

Conclusion: PTL significantly inhibits gallbladder cancer cell proliferation and induces apoptosis through the MAPK pathway, which is a potential molecular reagent for treating GBC. However, further exploration is needed to verify the antitumor effects of PTL and its intracellular signalling mechanism.

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