ArticleCells2022
Combination of Paclitaxel and PXR Antagonist SPA70 Reverses Paclitaxel-Resistant Non-Small Cell Lung Cancer.
Article in Cells, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Medications That Regulate Pregnane X Receptor: A Systematic Review of Current Evidence.Pharmacology research & perspectives · 2026Pooled it
- A microfluidic lung cancer-vascular tumor-on-a-chip model for precise evaluation of anti-invasion therapeutics.Clinical and experimental medicine · 2026Article
- From Screening to a Nanotechnological Platform: Cannabidiol-Chemotherapy Co-Loaded Lipid Nanocapsules for Glioblastoma Multiforme Treatment.Pharmaceutics · 2025Article
- Cytoplasmic PXR regulates glucose metabolism by binding mRNAs and modulating their stability.Nature structural & molecular biology · 2025Article
- Pregnane X receptor (PXR) as a prognostic marker and therapeutic target in kidney renal clear cell carcinoma (KIRC) via AMPK pathway regulation.Scientific reports · 2025Article
- Mechanisms and Therapeutic Advances of PXR in Metabolic Diseases and Cancer.International journal of molecular sciences · 2025Review
- Synergistic chemotherapy and phototherapy co-delivery nanoparticle preparation and anti-triple negative breast cancer study.RSC advances · 2025Article
- Tenacissoside G reverses paclitaxel resistance by inhibiting Src/PTN/P-gp signaling axis activation in ovarian cancer cells.Journal of natural medicines · 2025Article
- Salidroside Enhances the Sensitivity of Lung Cancer Cells to Paclitaxel by Regulating the Wnt/β-catenin Signaling Pathway.Current medical science · 2025Article
- First-in-Class Small Molecule Degrader of Pregnane X Receptor Enhances Chemotherapy Efficacy.Journal of medicinal chemistry · 2024Article
- Review
- Enhancement of paclitaxel production by Neopestalotiopsis vitis via optimization of growth conditions.PloS one · 2024Article
- Regulation of PXR in drug metabolism: chemical and structural perspectives.Expert opinion on drug metabolism & toxicologyReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Paclitaxel (PTX) is one of the most efficient drugs for late-stage non-small cell lung cancer (NSCLC) patients. However, most patients gradually develop resistance to PTX with long-term treatments. The identification of new strategies to reverse PTX resistance in NSCLC is crucially important for the treatment. PTX is an agonist for the pregnane X receptor (PXR) which regulates PTX metabolism. Antagonizing PXR, therefore, may render the NSCLC more sensitive to the PTX treatment. In this study, we investigated the PXR antagonist SPA70 and its role in PTX treatment of NSCLC. In vitro, SPA70 and PTX synergistically inhibited cell growth, migration and invasion in both paclitaxel-sensitive and paclitaxel-resistant A549 and H460 lung cancer cells. Mechanistically, we found PTX and SPA70 cotreatment disassociated PXR from ABCB1 (MDR1, P-gp) promoter, thus inhibiting P-gp expression. Furthermore, the combination regimen synergistically enhanced the interaction between PXR and Tip60, which abrogated Tip60-mediated α-tubulin acetylation, leading to mitosis defect, S-phase arrest and necroptosis/apoptosis. Combination of PXT and SPA70 dramatically inhibited tumor growth in a paclitaxel-resistant A549/TR xenograft tumor model. Taken together, we showed that SPA70 reduced the paclitaxel resistance of NSCLC. The combination regimen of PTX and SPA70 could be potential novel candidates for the treatment of taxane-resistant lung cancer.
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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.