ArticleMolecular cancer therapeutics2016
Vitamin D Enhances the Efficacy of Irinotecan through miR-627-Mediated Inhibition of Intratumoral Drug Metabolism.
Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Alkaloids mediated regulation of microRNA in cancer: molecular insights and emerging therapeutic strategies.Frontiers in oncology · 2026Review
- A Review of Food Bioactives That Can Modulate miRNA Profiles for Management of Colorectal Cancer.Foods (Basel, Switzerland) · 2025Review
- Understanding Cancer's Defense against Topoisomerase-Active Drugs: A Comprehensive Review.Cancers · 2024Review
- A Pilot Study of Paricalcitol plus Nanoliposomal Irinotecan and 5-FU/LV in Advanced Pancreatic Cancer Patients after Progression on Gemcitabine-Based Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- The Role of CYP3A in Health and Disease.Biomedicines · 2022Review
- Interplay of Vitamin D and CYP3A4 Polymorphisms in Endocrine Disorders and Cancer.Endocrinology and metabolism (Seoul, Korea) · 2022Review
- Review
- A Novel miRNA Screen Identifies miRNA-4454 as a Candidate Biomarker for Ventricular Fibrosis in Patients with Hypertrophic Cardiomyopathy.Biomolecules · 2021Article
- The Molecular Networks of microRNAs and Their Targets in the Drug Resistance of Colon Carcinoma.Cancers · 2021Review
- Pharmacokinetic Estimation Models-based Approach to Predict Clinical Implications for CYP Induction by Calcitriol in Human Cryopreserved Hepatocytes and HepaRG Cells.Pharmaceutics · 2021Article
- INTEDE: interactome of drug-metabolizing enzymes.Nucleic acids research · 2021Article
- Participation of MicroRNAs in the Treatment of Cancer with Phytochemicals.Molecules (Basel, Switzerland) · 2020Review
- RP11‑284F21.9 promotes lung carcinoma proliferation and invasion via the regulation of miR‑627‑3p/CCAR1.Oncology reports · 2020Article
- Vitamin D3 Is Transformed into 1,25(OH)2D3 by Triggering CYP3A11(CYP3A4) Activity and Hydrolyzing Midazolam.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Article
- NR2C2-uORF targeting UCA1-miR-627-5p-NR2C2 feedback loop to regulate the malignant behaviors of glioma cells.Cell death & disease · 2018Article
- miRNA-627 inhibits cell proliferation and cell migration, promotes cell apoptosis in prostate cancer cells through upregulating MAP3K1, PTPRK and SRA1.International journal of clinical and experimental pathology · 2018Article
- Alantolactone induces apoptosis, promotes STAT3 glutathionylation and enhances chemosensitivity of A549 lung adenocarcinoma cells to doxorubicin via oxidative stress.Scientific reports · 2017Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cytochrome P450 enzyme CYP3A4 is an important drug-metabolizing enzyme, and high levels of tumoral expression of CYP3A4 are linked to drug resistance. We investigated the function of vitamin D-regulated miR-627 in intratumoral CYP3A4 suppression and its role in enhancing the efficacy of chemotherapy. We found that miR-627 targets CYP3A4 and suppresses CYP3A4 expression in colon cancer cell lines. Furthermore, calcitriol (the active form of vitamin D) suppressed CYP3A4 expression by activating miR-627. As a result, calcitriol inhibited CYP3A4-mediated metabolism of irinotecan (a topoisomerase I inhibitor) in cancer cells. We show that calcitriol enhanced the efficacy of irinotecan in growth inhibition and apoptosis induction. When miR-627 is inhibited, calcitriol fails to enhance the activity of irinotecan. In addition, overexpression of miR-627 or siRNA knockdown of CYP3A4 enhanced the efficacy of irinotecan in growth inhibition and apoptosis induction. In contrast, overexpression of CYP3A4 abolished the effects of calcitriol on the activity of irinotecan. Using a nude mouse xenograft model, we demonstrated that calcitriol inhibited CYP3A4 and enhanced the in vivo antitumor activity of irinotecan without causing side effects. Our study identified a novel target for improving cancer therapy, i.e., modulating the intratumoral CYP3A4-mediated drug metabolism with vitamin D. This strategy could enhance the therapeutic efficacy without eliciting the side effects. Mol Cancer Ther; 15(9); 2086-95. ©2016 AACR.
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