ArticleCell death & disease2018
(S)-crizotinib reduces gastric cancer growth through oxidative DNA damage and triggers pro-survival akt signal.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 23 citations in OpenAlex.
- Clinical Significance of NUDT1 (MTH1) Across Cancer Types.International journal of molecular sciences · 2025Review
- Case Report: A rare case of MET-amplified gastric cancer with systemic metastasis: remarkable efficacy of crizotinib and the role of precision medicine.Frontiers in oncology · 2025Article
- Review
- Synergism of FAK and ROS1 inhibitors in the treatment ofInternational journal of biological sciences · 2023Article
- Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Kinase Inhibitor Screening DisplayedPharmaceutics · 2022Article
- Interplay of Developmental Hippo-Notch Signaling Pathways with the DNA Damage Response in Prostate Cancer.Cells · 2022Review
- Phosphoproteomics reveals that cinobufotalin promotes intrahepatic cholangiocarcinoma cell apoptosis by activating the ATM/CHK2/p53 signaling pathway.Frontiers in oncology · 2022Article
- In Defense of the Nucleus: NUDT1 and Oxidative DNA Damage in Pulmonary Arterial Hypertension.American journal of respiratory and critical care medicine · 2021Article
- Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.Frontiers in oncology · 2021Review
- Crizotinib and Doxorubicin Cooperatively Reduces Drug Resistance by Mitigating MDR1 to Increase Hepatocellular Carcinoma Cells Death.Frontiers in oncology · 2021Article
- Inhibitors of DNA Glycosylases as Prospective Drugs.International journal of molecular sciences · 2020Review
- Gastroprotective effects of Kangfuxin against water-immersion and restraint stress-induced gastric ulcer in rats: roles of antioxidation, anti-inflammation, and pro-survival.Pharmaceutical biology · 2019Article
- Novel Crizotinib-GnRH Conjugates Revealed the Significance of Lysosomal Trapping in GnRH-Based Drug Delivery Systems.International journal of molecular sciences · 2019Article
- Ponatinib Inhibits Proliferation and Induces Apoptosis of Liver Cancer Cells, but Its Efficacy Is Compromised by Its Activation on PDK1/Akt/mTOR Signaling.Molecules (Basel, Switzerland) · 2019Article
- Di-n-butyl phthalate epigenetically induces reproductive toxicity via the PTEN/AKT pathway.Cell death & disease · 2019Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gastric cancer (GC), a common gastrointestinal malignancy worldwide, has poor prognosis and frequent recurrence. There is a great need to identify effective therapy for GC. Crizotinib is a multi-targeted, clinically available oral tyrosine kinase inhibitor approved for lung cancer, but its use for the highly heterogeneous disease of GC is unknown. The goal of this study was to investigate the anti-cancer mechanisms of the (S)-crizotinib in inhibiting GC growth. Human GC cell lines (SGC-7901 and BGC-823) and the (S)-crizotinib-resistant BGC-823/R were cultured for determining the effects of (S)-crizotinib on cell viability, apoptosis, oxidant generation, and cell cycle progression. Involvement of ROS, Akt signaling, MTH1, and DNA damage was tested with respective pharmacological blockade. The in vivo anti-tumor effects of (S)-crizotinib were determined using xenograft tumor mice. Results indicated that (S)-crizotinib decreased GC cell viability, induced growth arrest and apoptosis, and increased levels of γH2AX and Ser1981-phosphorylated ATM, which were inhibited by NAC. The anti-cancer mechanism of (S)-crizotinib was independent of MTH1. Moreover, ATM-activated Akt, a pro-survival signal, whose inhibition further enhanced (S)-crizotinib-induced inhibition of GC cell growth and tumor growth in xenograft mice, and re-sensitized resistant GC cells to (S)-crizotinib. (S)-crizotinib reduced GC cell and tumor growth through oxidative DNA damage mechanism and triggered pro-survival Akt signaling. We conclude that inclusion of Akt inhibition (to block the survival signaling) with (S)-crizotinib may provide an effective and novel combination therapy for GC in the clinical setting.
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