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CM-33

IL-17 signaling and Dahuang-Mudan Decoction in gemcitabine resistance of

pancreatic cancer

3
#,3
Muhammad Waqas #,1,2 Ching Sheng Tay , Der-Yen Lee , Chao-Jung Chen , Huang-Wei
3
1
3
Lo , Ping Chuang , Hen-Hong Chang , Yu-Huei Liu* ,1,3,4
3

1 Drug Development Center, China Medical University, Taichung, Taiwan
2 Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China
Medical University, Taichung, Taiwan
3 Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan
4 Department of Medical Research, China Medical University Hospital, Taichung, China
Medical University
* E-mail: yuhueiliu@mail.cmu.edu.tw

Abstract
Pancreatic cancer (PC) remains one of the most aggressive malignancies, characterized by
late diagnosis, limited treatment options, and poor survival outcomes. Standard chemotherapy
with gemcitabine provides only modest benefits and is frequently constrained by toxicity.
Recent evidence indicates that gut dysbiosis, triggered by disruption of enteric epithelial
interleukin 17 (IL-17) signaling promotes PC progression and gemcitabine resistance through
systemic immunomodulation. However, the roles and crosstalk among IL-17 family members
in modulating drug response remain incompletely understood. Here, we demonstrate that
distinct IL-17 cytokines exert differential effects on pancreatic cancer cells carrying diverse
KRAS mutations. These findings suggest a context-dependent role of IL-17 signaling in
shaping tumor behavior and chemotherapy response. We further discover that the traditional
Chinese medicine formula Dahuang-Mudan Decoction (DHMD) effectively enhances
gemcitabine sensitivity through improving gemcitabine-induced gut dysbiosis, highlighting its
potential as an integrative therapeutic approach. Our current results underscore the
heterogeneity of IL-17 family–mediated regulation of gemcitabine resistance and provide
preclinical support for combining DHMD with standard chemotherapy to improve PC treatment.

Keywords: Pancreatic cancer; Gemcitabine resistance; IL-17; Dahuang Mudan Decoction