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

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-resista...

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Bibliographic Details
Published in:Computational and structural biotechnology journal 2024-12, Vol.23, p.3634-3650
Main Authors: Shi, Saimeng, Ye, Longyun, Jin, Kaizhou, Yu, Xianjun, Guo, Duancheng, Wu, Weiding
Format: Article
Language:English
Subjects:
C3aR antagonist
Complement C3a
Gemcitabine resistance
Neoadjuvant therapy
Pancreatic cancer
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Summary: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. [Display omitted]
ISSN:2001-0370
2001-0370
DOI:10.1016/j.csbj.2024.09.032