ArticleCancer cell international2023
In vitro co-culture systems of hepatic and intestinal cells for cellular pharmacokinetic and pharmacodynamic studies of capecitabine against colorectal cancer.
Article in Cancer cell international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
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- Anti-Colon Cancer Effects of Lysate from Potential Probiotic Yeast Strains Derived from Human Breast Milk.Probiotics and antimicrobial proteins · 2025Article
- Novel emerging cell and organoid systems for the study of drug metabolism and toxicity in humans.Drug metabolism and disposition: the biological fate of chemicals · 2025Review
- Roles of Wnt ligands and receptors in oral squamous cell carcinoma.Journal of Zhejiang University. Science. B · 2025Review
- Differential expression of capecitabine-related metabolic enzymes in hepatocellular carcinoma and its clinical value: a retrospective cohort study.Discover oncology · 2025Article
- Examination of the effects of capecitabine treatment on the HT-29 colorectal cancer cell line and HCG 11, HCG 15, and HCG 18 lncRNAs in CRC patients before and after chemotherapy.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- A comprehensive review on computational metabolomics: Advancing multiscale analysis throughComputational and structural biotechnology journal · 2025Review
- Advanced prodrug strategies in nucleoside analogues targeting the treatment of gastrointestinal malignancies.Frontiers in cell and developmental biology · 2023Review
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAs a prodrug of 5-fluorouracil (5-FU), orally administrated capecitabine (CAP) undergoes preliminary conversion into active metabolites in the liver and then releases 5-FU in the gut to exert the anti-tumor activity. Since metabolic changes of CAP play a key role in its activation, a single kind of intestinal or hepatic cell can never be used in vitro to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) nature. Hence, we aimed to establish a novel in vitro system to effectively assess the PK and PD of these kinds of prodrugs.
methodsCo-culture cellular models were established by simultaneously using colorectal cancer (CRC) and hepatocarcinoma cell lines in one system. Cell Counting Kit-8 (CCK-8) and flow cytometric analysis were used to evaluate cell viability and apoptosis, respectively. Apoptosis-related protein expression levels were measured using western blot analysis. A selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for cellular PK in co-culture models.
resultsCAP had little anti-proliferative effect on the five monolayer CRC cell lines (SW480, LoVo, HCT-8, HCT-116 and SW620) or the hepatocarcinoma cell line (HepG2). However, CAP exerted marked anti-tumor activities on each of the CRC cell lines in the co-culture models containing both CRC and hepatocarcinoma cell lines, although its effect on the five CRC cell lines varied. Moreover, after pre-incubation of CAP with HepG2 cells, the culture media containing the active metabolites of CAP also showed an anti-tumor effect on the five CRC cell lines, indicating the crucial role of hepatic cells in the activation of CAP.
conclusionThe simple and cost‑effective co-culture models with both CRC and hepatocarcinoma cells could mimic the in vivo process of a prodrug dependent on metabolic conversion to active metabolites in the liver, providing a valuable strategy for evaluating the PK and PD characteristics of CAP-like prodrugs in vitro at the early stage of drug development.
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