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PA-MSHA exerts potent activity against cetuximab-resistant colorectal cancer through the miR-7-5p/Akt3/Wnt-ß-catenin pathway.
Zhang, Huanhuan; Du, Fei; Li, Dan; Zhang, Jiayun; Shan, Wulin.
Afiliación
  • Zhang H; Department of Cancer Epigenetics Program, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  • Du F; Department of Laboratory Diagnostics, The First People's Hospital of Hefei City, The Third Affiliated Hospital of Anhui Medical University, Hefei, China.
  • Li D; Department of Laboratory Diagnostics, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  • Zhang J; Department of Laboratory Diagnostics, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  • Shan W; Department of Laboratory Diagnostics, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Transl Cancer Res ; 13(8): 4441-4458, 2024 Aug 31.
Article en En | MEDLINE | ID: mdl-39262485
ABSTRACT

Background:

The prognosis and survival of individuals with cetuximab-resistant colorectal cancer (CRC) remain severely impacted by therapy for this disease. The study investigated the underlying mechanisms of Pseudomonas aeruginosa-mannose sensitive hemagglutinin (PA-MSHA), a type of therapeutic biological product approved in China, for cetuximab-resistant CRC.

Methods:

Cell proliferation, apoptosis, migration and invasion were detected by cell counting kit-8 (CCK-8) assay, flow cytometry, wound healing assay and transwell assay. Massively parallel sequencing of cetuximab-resistant CRC cells with PA-MSHA treatment was used to screen the differential expression profile of miRNAs. The directly target gene of miR-7-5p was revealed by dual luciferase assay. Apoptosis and invasion related proteins were detected by Western blot.

Results:

PA-MSHA could successfully stop the migrating and invading of cetuximab-resistant CRC cells while also inducing apoptosis. Tumor-bearing experiments in nude mice showed that PA-MSHA slowed tumor growth and lengthened mouse life. The sequencing data showed that miR-7-5p was considerably upregulated after PA-MSHA treatment. As anticipated, miR-7-5p overexpression improved PA-MSHA's anticancer properties both in vitro and in vivo. The target gene of miR-7-5p was confirmed to be Akt3 by dual luciferase assay, and Akt3 silencing undid the inhibition of PA-MSHA efficacy caused by miR-7-5p downregulation. Additionally, PA-MSHA therapy significantly reduced the activation of Wnt-ß-catenin pathway, and Akt3 expression was positively linked with several important Wnt-ß-catenin pathway genes, including Wnt and CTNNB1. Finally, we discovered that patients with CRC who had developed cetuximab resistance or disease progression had remarkably decreased serum miR-7-5p levels.

Conclusions:

PA-MSHA controlled the miR-7-5p/Akt3/Wnt-ß-catenin pathway to provide substantial efficacy against cetuximab-resistant CRC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Transl Cancer Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Transl Cancer Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: China