Evidence map›Paper›PMID 42113266›Full record

ArticleCancer chemotherapy and pharmacology2026

Synergistic anti-tumor activity of andrographolide and gemcitabine in intrahepatic cholangiocarcinoma through inhibition of RRM2 and the JAK/STAT3 pathway.

Qinghang Song, Chunjuan Yu, Fulin Sun, Wenbo Wang, Ziyuan Wen, Ruolan Chen, Yiming Wang, Haoran Wang, Zhenxiang Wang, Bing Li and 1 more

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Article in Cancer chemotherapy and pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Qinghang SongSchool of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Chunjuan YuSchool of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Fulin SunSchool of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Wenbo WangSchool of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Ziyuan WenSchool of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Ruolan ChenSchool of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Yiming WangSchool of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Haoran WangSchool of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Zhenxiang WangSchool of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Bing LiSchool of Basic Medicine, Qingdao University, Qingdao, 266071, China. libing_516@qdu.edu.cn.
Lina YangSchool of Basic Medicine, Qingdao University, Qingdao, 266071, China. yanglina@qdu.edu.cn.

Funding

National Natural Science Foundation of China No.81803895National Training Program of Innovation and Entrepreneurship 202411065010Natural Science Foundation of Shandong Province ZR2024MH266
6 · The paper itself

Abstract

purposeIntrahepatic cholangiocarcinoma (ICC) is a lethal malignancy frequently characterized by intrinsic resistance to standard gemcitabine (Gem) chemotherapy. This study aimed to investigate whether andrographolide (Andro) could sensitize intrinsically gemcitabine-resistant ICC cells to gemcitabine and to explore the underlying molecular mechanisms.

methodsNaturally Gem-resistant ICC cell lines (HUCCT-1 and QBC-939) were treated with Andro, Gem, or their combination. Synergistic effects were quantified using the Chou-Talalay method. Anti-tumor efficacy was assessed via CCK-8, colony formation, EdU incorporation, wound healing, and Transwell invasion assays. ROS accumulation, apoptosis, mitochondrial membrane potential, and cell-cycle distribution were assessed by fluorescence microscopy and flow cytometry, as appropriate. Molecular targets were identified using molecular docking, RT-qPCR, and Western blotting.

resultsAndro and Gem exhibited strong synergistic anti-tumor activity (Combination Index < 1.0) in both cell lines. The combination significantly suppressed proliferation, motility, and epithelial-mesenchymal transition. Mechanistically, the synergy was driven by a surge in intracellular ROS, triggering mitochondrial apoptosis and G1/S phase arrest. Furthermore, Ribonucleotide-diphosphate reductase subunit M2 was identified as a candidate molecular target associated with the effects of andrographolide, leading to its downregulation and the subsequent inactivation of the JAK/STAT3 signaling pathway.

conclusionAndrographolide overcomes intrinsic Gem resistance in ICC, potentially through modulation of the RRM2/JAK/STAT3 axis. This combination therapy represents a promising strategy for treating chemoresistant intrahepatic cholangiocarcinoma.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBile Duct NeoplasmsCholangiocarcinomaDeoxycytidineDiterpenesRibonucleoside Diphosphate ReductaseApoptosisCell Line, TumorCell MovementCell ProliferationDrug Resistance, NeoplasmDrug SynergismGemcitabineHumansJanus KinasesMembrane Potential, MitochondrialandrographolideDeoxycytidineDiterpenesGemcitabineJanus KinasesRibonucleoside Diphosphate Reductaseribonucleotide reductase M2STAT3 protein, humanSTAT3 Transcription FactorAndrographolideGemcitabineIntrahepatic cholangiocarcinomaJAK/STAT3 pathwayRRM2Synergistic effect

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.