ArticleCancer letters2018
SIS3, a specific inhibitor of Smad3 reverses ABCB1- and ABCG2-mediated multidrug resistance in cancer cell lines.
Article in Cancer letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Long-term dynamic profiles of cognitive kinases induced by different learning protocols.bioRxiv : the preprint server for biology · 2025Article
- Distinct BMP-Smad signaling outputs confer diverse functions in dental mesenchyme.Development (Cambridge, England) · 2025Article
- Targeting Smad3 Phosphorylation Attenuates Anastomotic Intimal Hyperplasia and Perigraft Fibrosis in Decellularized Tissue-Engineered Vascular Grafts.Biomaterials research · 2025Article
- Probing the binding hypothesis of Smad3 modulators by molecular dynamic simulations for Atherosclerosis Cardiovascular Disease (ASCVD).PloS one · 2025Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Macrophage pyroptosis promotes synovial fibrosis through the HMGB1/TGF- β1 axis: an in vivo and in vitro study.In vitro cellular & developmental biology. Animal · 2023Article
- Hydroxygenkwanin Improves the Efficacy of Cytotoxic Drugs in ABCG2-Overexpressing Multidrug-Resistant Cancer Cells.International journal of molecular sciences · 2022Article
- The multi-targeted tyrosine kinase inhibitor SKLB610 resensitizes ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- EZH2-triggered methylation of SMAD3 promotes its activation and tumor metastasis.The Journal of clinical investigation · 2022Article
- Co-delivery of doxorubicin and SIS3 by folate-targeted polymeric micelles for overcoming tumor multidrug resistance.Drug delivery and translational research · 2022Article
- ABCB1 and ABCG2 restricts the efficacy of gedatolisib (PF-05212384), a PI3K inhibitor in colorectal cancer cells.Cancer cell international · 2021Article
- Fzd2 Contributes to Breast Cancer Cell Mesenchymal-Like Stemness and Drug Resistance.Oncology research · 2020Article
- M3814, a DNA-PK Inhibitor, Modulates ABCG2-Mediated Multidrug Resistance in Lung Cancer Cells.Frontiers in oncology · 2020Article
- Sitravatinib, a Tyrosine Kinase Inhibitor, Inhibits the Transport Function of ABCG2 and Restores Sensitivity to Chemotherapy-Resistant Cancer CellsFrontiers in oncology · 2020Article
- Long-term dynamic profiles of cognitive kinases induced by different learning protocols.Learning & memory (Cold Spring Harbor, N.Y.)Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
One of the major challenges in cancer chemotherapy is the development of multidrug resistance phenomenon attributed to the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2 in cancer cells. Therefore, re-sensitizing MDR cancer cells to chemotherapy by directly inhibiting the activity of ABC transporters has clinical relevance. Unfortunately, previous attempts of developing clinically applicable synthetic inhibitors have failed, mostly due to problems associated with toxicity and unforeseen drug-drug interactions. An alternative approach is by repositioning drugs with known pharmacological properties as modulators of ABCB1 and ABCG2. In this study, we discovered that the transport function of ABCB1 and ABCG2 is strongly inhibited by SIS3, a specific inhibitor of Smad3. More importantly, SIS3 enhances drug-induced apoptosis and resensitizes ABCB1- and ABCG2-overexpressing cancer cells to chemotherapeutic drugs at non-toxic concentrations. These findings are further supported by ATPase assays and by a docking analysis of SIS3 in the drug-binding pockets of ABCB1 and ABCG2. In summary, we revealed an additional action of SIS3 that re-sensitizes MDR cancer cells and a combination therapy with this drug and other chemotherapeutic agents may be beneficial for patients with MDR tumors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.