The complement C3a/C3aR pathway is associated with treatment resistance to gemcitabine-based neoadjuvant therapy in pancreatic cancer

Autor: Saimeng Shi, Longyun Ye, Kaizhou Jin, Xianjun Yu, Duancheng Guo, Weiding Wu
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Computational and Structural Biotechnology Journal, Vol 23, Iss , Pp 3634-3650 (2024)
Druh dokumentu: article
ISSN: 2001-0370
DOI: 10.1016/j.csbj.2024.09.032
Popis: Gemcitabine is a standard first-line drug for pancreatic cancer chemotherapy. Nevertheless, gemcitabine resistance is common and significantly limits its therapeutic efficacy, impeding advancements in pancreatic cancer treatment. In this study, through a comprehensive analysis of gemcitabine-resistant cell lines and patient samples, 39 gemcitabine resistance-associated risk genes were identified, and two distinct gemcitabine response-related phenotypes were delineated. Through a combination of bioinformatics analysis and in vivo and in vitro experiments, we identified the C3a/C3aR signaling pathway as a pivotal player in the development of gemcitabine resistance in pancreatic cancer. We found that activation of the C3a/C3aR signaling pathway promoted the proliferation, migration and gemcitabine resistance of pancreatic cancer cells, while the C3aR antagonist SB290157 effectively counteracted these effects by impeding the activation of the C3a/C3aR pathway. Our study reveals the fundamental role of complement C3a in the progression of pancreatic cancer, suggesting that complement C3a may serve as a promising biomarker in pancreatic cancer.
Databáze: Directory of Open Access Journals