ArticleJournal of translational medicine2022
Inhibition of XPO1 with KPT-330 induces autophagy-dependent apoptosis in gallbladder cancer by activating the p53/mTOR pathway.
Article in Journal of translational medicine, 2022. 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, 25 citations in OpenAlex.
- Phase I/II Trial of Exportin 1 Inhibitor Selinexor plus Docetaxel in Previously Treated, Advanced KRAS-Mutant Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Splicing-mediated control of hnRNPD isoform switching by SRSF2 drives PD-L1-dependent immune evasion in gallbladder cancer.Oncogene · 2026Article
- C2ORF68 stabilizes SIVA1 to upregulate BCL-2 and suppress apoptosis in gallbladder cancer.Cell death discovery · 2026Article
- Exploring the therapeutic potential of Lupeol isolated from Ochrosia elliptica Labill. leaves in polycystic ovarian syndrome.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Therapeutic synergies that overcome carboplatin resistance in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- Combination effect of Exportin 1 inhibitor (KPT-335) with doxorubicin or vincristine in canine lymphoma cell lines.The Journal of veterinary medical science · 2026Article
- Selinexor, a selective inhibitor of nuclear export, shows anti-proliferative and anti-migratory effects on male germ cells in vitro.BMC pharmacology & toxicology · 2025Article
- NSUN6 Promotes Gastric Cancer Progression by Stabilizing CEBPZ mRNA in a mApplied biochemistry and biotechnology · 2025Article
- HLF transactivatesScience advances · 2025Article
- Development and challenges in the treatment of advanced gallbladder cancer (Review).Oncology letters · 2025Review
- Autophagy modulates glioblastoma cell sensitivity to Selinexor-mediated XPO1 inhibition.Neuro-oncology · 2025Article
- Positive Feedback Regulation between KLF5 and XPO1 Promotes Cell Cycle Progression of Basal like Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Prognostic and functional role of the nuclear export receptor 1 (XPO1) in gastrointestinal cancers: a potential novel target?Molecular biology reports · 2024Review
- BRD9 promotes the progression of gallbladder cancer via CST1 upregulation and interaction with FOXP1 through the PI3K/AKT pathway and represents a therapeutic target.Gene therapy · 2024Article
- Article
- The nuclear export protein exportin-1 in solid malignant tumours: From biology to clinical trials.Clinical and translational medicine · 2024Review
- Acylcarnitines promote gallbladder cancer metastasis through lncBCL2L11-THOC5-JNK axis.Journal of translational medicine · 2024Article
- BOP1 contributes to the activation of autophagy in polycystic ovary syndrome via nucleolar stress response.Cellular and molecular life sciences : CMLS · 2024Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGallbladder cancer (GBC) is a highly aggressive malignant cancer in the biliary system with poor prognosis. XPO1 (chromosome region maintenance 1 or CRM1) mediates the nuclear export of several proteins, mainly tumor suppressors. Thus, XPO1 functions as a pro-oncogenic factor. KPT-330 (Selinexor) is a United States Food and Drug Administration approved selective inhibitor of XPO1 that demonstrates good therapeutic effects in hematologic cancers. However, the function of XPO1 and the effect of KPT-330 have not been reported in GBC.
methodsWe analyzed the correlation between XPO1 expression levels by q-PCR and clinical features of GBC patients. Cell proliferation assays were used to analyze the in vitro antitumor effects of XPO1 inhibitor KPT-330. mRNA sequencing was used to explore the underlying mechanisms. Western blot was performed to explore the relationship between apoptosis and autophagy. The in vivo antitumor effect of KPT-330 was investigated in a nude mouse model of gallbladder cancer.
resultsWe found that high expression of XPO1 was related to poor prognosis of GBC patients. We observed that XPO1 inhibitor KPT-330 inhibited the proliferation of GBC cells in vitro. Furthermore, XPO1 inhibitor KPT-330 induced apoptosis by reducing the mitochondrial membrane potential and triggering autophagy in NOZ and GBC-SD cells. Indeed, XPO1 inhibitor KPT-330 led to nuclear accumulation of p53 and activated the p53/mTOR pathway to regulate autophagy-dependent apoptosis. Importantly, KPT-330 suppressed tumor growth with no obvious toxic effects in vivo.
conclusionXPO1 may be a promising prognostic indicator for GBC, and KPT-330 appears to be a potential drug for treating GBC effectively and safely.
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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.