ArticleMolecular biology reports2012
Synergistic inhibitory effects by the combination of gefitinib and genistein on NSCLC with acquired drug-resistance in vitro and in vivo.
Article in Molecular biology reports, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed, 43 citations in OpenAlex.
- Self-Assembled Gefitinib Nanosuspension Prepared via Hummer Acoustic Resonance Technology: Enhanced Dissolution, In Vitro Anticancer Activity and Long-Term Stability.Pharmaceutics · 2026Article
- Pharmacodynamics and safety in relation to dose and response of plant flavonoids in treatment of cancers.Inflammopharmacology · 2025Review
- Genistein as a Chemo-modulatory Agent: Exploring its Potential in Chemosensitization and Combinatorial Therapeutic Strategies for Cancer Treatment.Current topics in medicinal chemistry · 2025Review
- Drug Combination Studies of Isoquinolinone AM12 with Curcumin or Quercetin: A New Combination Strategy to Synergistically Inhibit 20S Proteasome.International journal of molecular sciences · 2024Article
- Bio-Inspired Nanodelivery Platform: Platelet Membrane-Cloaked Genistein Nanosystem for Targeted Lung Cancer Therapy.International journal of nanomedicine · 2024Article
- Overexpression of PELP1 in Lung Adenocarcinoma Promoted EPathology oncology research : POR · 2021Article
- Alleviation of Multidrug Resistance by Flavonoid and Non-Flavonoid Compounds in Breast, Lung, Colorectal and Prostate Cancer.International journal of molecular sciences · 2020Review
- Inhibitory effects of genistein in combination with gefitinib on the hepatocellular carcinoma Hep3B cell line.Experimental and therapeutic medicine · 2019Article
- MS-275 potentiates the effect of YM-155 in lung adenocarcinoma via survivin downregulation induced by miR-138 and miR-195.Thoracic cancer · 2019Article
- Structure-Based Classification and Anti-Cancer Effects of Plant Metabolites.International journal of molecular sciences · 2018Review
- Genistein suppresses retinoblastoma cell viability and growth and induces apoptosis by upregulating miR-145 and inhibiting its target ABCE1.Molecular vision · 2017Article
- Article
- A multi-targeted approach to suppress tumor-promoting inflammation.Seminars in cancer biology · 2015Review
- Sustained proliferation in cancer: Mechanisms and novel therapeutic targets.Seminars in cancer biology · 2015Review
- Genistein and cancer: current status, challenges, and future directions.Advances in nutrition (Bethesda, Md.) · 2015Review
- Dietary agents for prevention and treatment of lung cancer.Cancer letters · 2015Review
- Synthetic genistein glycosides inhibiting EGFR phosphorylation enhance the effect of radiation in HCT 116 colon cancer cells.Molecules (Basel, Switzerland) · 2014Article
- Resveratrol and genistein inhibition of rat isolated gastrointestinal contractions and related mechanisms.World journal of gastroenterology · 2014Article
- Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In clinical practice, most patients with non small cell lung cancer (NSCLC) who respond to tyrosine kinase inhibitors eventually progress because of an acquired resistance mutation, T790M, in epidermal growth factor receptor (EGFR). Thus, it is important to identify a new drug to reduce resistance. The aim of this study was to test whether genistein combined with gefitinib is effective against NSCLC in a cell line carrying T790M, and to clarify the underlying mechanisms. The human lung cancer cell line H1975 was used as an in vitro and in vivo model. Cells were treated with gefitinib, genistein, or a combination at a range of concentrations. Cell proliferation was calculated to assess the anticancer effects of the compounds in vitro. Flow cytometry and Western blotting were employed to determine the inhibitory effects on proliferation and the induction of apoptosis. The in vivo effects of the compounds were examined using a xenografted nude mouse model for validation. Gefitinib together with genistein enhanced both growth inhibition and apoptosis; however, the greatest synergistic effect was observed at low concentrations. p-EGFR, p-Akt, and p-mTOR expressions in vitro were reduced more by the combined use of the drugs, whereas caspase-3 and PARP activities were increased. Significantly more tumor growth inhibition was detected following combination treatment in the in vivo model. These findings suggest that genistein enhanced the antitumor effects of gefitinib in a NSCLC cell line carrying the T790M mutation. This synergistic activity may be due to increased inhibition of the downstream molecular and pro-apoptotic effects of EGFR.
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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.