ArticleCarcinogenesis2021
Andrographis overcomes 5-fluorouracil-associated chemoresistance through inhibition of DKK1 in colorectal cancer.
Article in Carcinogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 29 citations in OpenAlex.
- DKN-01 and tislelizumab as second-line therapy in DKK1-high gastroesophageal adenocarcinoma: DisTinGuish trial part B.Nature communications · 2025Trial
- Andrographis restrains the progression of colorectal cancer by inhibiting the KLF3/LEMD1 axis.Functional & integrative genomics · 2026Article
- Cancer-associated fibroblast secreted DKK1 promotes the immunosuppressive tumor microenvironment and colorectal cancer resistance to chemotherapy.Cancer letters · 2025Article
- Oligomeric Proanthocyanidins Reverse Lenvatinib Resistance in Hepatocellular Carcinoma Through ITGA3-Mediated Pathway.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Metformin reverses 5-FU chemoresistance by downregulating DKK1, WNT5A, and ABCB1 expressions in gastric cancer: An experimental and bioinformatic study.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Dissecting the opposing regulatory functions of endogenous nitric oxide production in colorectal cancer initiation, adaptive immune response alterations, and ferroptosis execution.Oncology reviews · 2025Review
- Current Evidence on Molecular Mechanisms of Andrographolide in Cancer.Current medicinal chemistry · 2025Review
- Andrographolide sensitizes glioma to temozolomide by inhibiting DKK1 expression.British journal of cancer · 2024Article
- Combined treatment with Aronia berry extract and oligomeric proanthocyanidins exhibit a synergistic anticancer efficacy through LMNB1-AKT signaling pathways in colorectal cancer.Molecular carcinogenesis · 2024Article
- Aronia Berry Extract Modulates MYD88/NF-kB/P-Glycoprotein Axis to Overcome Gemcitabine Resistance in Pancreatic Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Article
- The potential therapeutic effect of melatonin in oxaliplatin combination therapy against chemoresistant colorectal cancer cells.Molecular biology reports · 2024Article
- Article
- Ginseng mediates its anticancer activity by inhibiting the expression of DNMTs and reactivating methylation-silenced genes in colorectal cancer.Carcinogenesis · 2023Article
- Andrographis modulates cisplatin resistance in lung cancer via miR-155-5p/SIRT1 axis.Functional & integrative genomics · 2023Article
- Curcumin and Andrographis Exhibit Anti-Tumor Effects in Colorectal Cancer via Activation of Ferroptosis and Dual Suppression of Glutathione Peroxidase-4 and Ferroptosis Suppressor Protein-1.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Andrographis Reverses Gemcitabine Resistance through Regulation of ERBB3 and Calcium Signaling Pathway in Pancreatic Ductal Adenocarcinoma.Biomedicines · 2023Article
- Propofol-Induced miR-493-3p Inhibits Growth and Invasion of Gastric Cancer through Suppression of DKK1-Mediated Wnt/Disease markers · 2023Article
- Targeting FTO Suppresses Pancreatic Carcinogenesis via Regulating Stem Cell Maintenance and EMT Pathway.Cancers · 2022Article
- Berberine Overcomes Gemcitabine-Associated Chemoresistance through Regulation of Rap1/PI3K-Akt Signaling in Pancreatic Ductal Adenocarcinoma.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Low CPEB1 levels may predict the benefit of 5-fluorouracil treatment in patients with colon or stomach adenocarcinoma.Journal of gastrointestinal oncology · 2022Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths in the USA. 5-Fluorouracil (5FU)-based chemotherapeutic drug remains a mainstay of CRC treatment. Unfortunately, ~50-60% of patients eventually develop resistance to 5FU, leading to poor survival outcomes. Our previous work revealed that andrographis enhanced 5FU-induced anti-cancer activity, but the underlying mechanistic understanding largely remains unclear. In this study, we first established 5FU-resistant (5FUR) CRC cells and observed that combined treatment with andrographis-5FU in 5FUR cells exhibited superior effect on cell viability, proliferation, and colony formation capacity compared with individual treatments (P < 0.001). To identify key genes and pathways responsible for 5FU resistance, we analyzed genome-wide transcriptomic profiling data from CRC patients who either responded or did not respond to 5FU. Among a panel of differentially expressed genes, Dickkopf-1 (DKK1) overexpression was a critical event for 5FU resistance. Moreover, andrographis significantly downregulated 5FU-induced DKK1 overexpression, accompanied with enhanced anti-tumor effects by abrogating downstream Akt-phosphorylation. In line with in vitro findings, andrographis enhanced 5FU-induced anti-cancer activity in mice xenografts and patient-derived tumoroids (P < 0.01). In conclusion, our data provide novel evidence for andrographis-mediated reversal of 5FU resistance, highlighting its potential role as an adjunct to conventional chemotherapy in CRC.
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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.