ArticleBMC cancer2018
Activation of LXRɑ/β by cholesterol in malignant ascites promotes chemoresistance in ovarian cancer.
Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 55 citations in OpenAlex.
- Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models.Cancer medicine · 2026Article
- Molecular and cellular landscapes of the immune microenvironment and multiomic biomarker-sets in platinum-resistant recurrent ovarian cancers.Journal of ovarian research · 2026Review
- The emerging role of cholesterol metabolism in gynecologic cancer development and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Targeting Mitochondrial Cholesterol Efflux via TCF21/ABCA10 Pathway to Enhance Cisplatin Efficacy in Ovarian Cancer.Biochemical genetics · 2025Article
- Alisol Triterpenoids Exhibit Triple Modulatory Mechanisms on the Cell Membrane to Overcome Cancer Multidrug Resistance.Drug design, development and therapy · 2025Article
- Malignancy of Malignant Ascites: A Comprehensive Review of Interplay between Biochemical Variables, Tumor Microenvironment and Growth Factors.Asian Pacific journal of cancer prevention : APJCP · 2024Review
- Why make it if you can take it: review on extracellular cholesterol uptake and its importance in breast and ovarian cancers.Journal of experimental & clinical cancer research : CR · 2024Review
- Cell-free ascites from ovarian cancer patients induces Warburg metabolism and cell proliferation through TGFβ-ERK signaling.GeroScience · 2024Article
- Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.International journal of biological sciences · 2024Review
- Novel players in the development of chemoresistance in ovarian cancer: ovarian cancer stem cells, non-coding RNA and nuclear receptors.Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Regulating Cholesterol in Tumorigenesis: A Novel Paradigm for Tumor Nanotherapeutics.International journal of nanomedicine · 2024Review
- Prediction of Chemoresistance-How Preclinical Data Could Help to Modify Therapeutic Strategy in High-Grade Serous Ovarian Cancer.Current oncology (Toronto, Ont.) · 2023Review
- Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins.International journal of molecular sciences · 2023Review
- Identification of a cholesterol metabolism-related prognostic signature for multiple myeloma.Scientific reports · 2023Article
- Review
- Dysregulation of Cholesterol Homeostasis in Ovarian Cancer.Current oncology (Toronto, Ont.) · 2023Review
- Emerging Insights into Liver X Receptor α in the Tumorigenesis and Therapeutics of Human Cancers.Biomolecules · 2023Review
- Associations of novel serum lipid index with epithelial ovarian cancer chemoresistance and prognosis.Frontiers in oncology · 2023Article
- Metabolic reprogramming of three major nutrients in platinum-resistant ovarian cancer.Frontiers in oncology · 2023Review
- Atorvastatin improves cisplatin sensitivity through modulation of cholesteryl ester homeostasis in breast cancer cells.Discover oncology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe purpose of this study was to investigate the role of malignant ascites tumor microenvironment in ovarian cancer progression and chemoresistance.
methodsA total of 45 patients with ovarian cancer and three benign ascites were collected at the time of clinical intervention. Ascites cholesterol levels were quantitated using cholesterol quantitation kit and recurrence free survival (RFS) of ovarian cancer patients were collected. The sensitivity of ovarian cancer cells to cisplatin (CDDP) and paclitaxel (PAC) were assessed by viability assay, flow cytometry and protein expression. Receiver operating characteristics (ROC) curve and Youden index analysis were applied to calculate the optimal cut-off values for ascites cholesterol. Kaplan-Meier curve were applied to compare RFS between high and low ascites cholesterol levels in ovarian cancer patients.
resultsHere we show that cholesterol is elevated in malignant ascites and modulates the sensitivity of ovarian cancer cells to CDDP and PAC by upregulating the expression of drug efflux pump proteins, ABCG2 and MDR1, together with upregulation of LXRɑ/β, the cholesterol receptor. Transfection of LXRɑ/β siRNA inhibited cholesterol-induced chemoresistance and upregulation of MDR1. In addition, the cholesterol level in malignant ascites was negatively correlated with number of CDDP-induced apoptotic cell death, but not with that of PAC-induced apoptotic cell death. Cholesterol depletion by methyl beta cyclodextrin (MβCD) inhibited malignant ascites-induced chemoresistance to CDDP and upregulation of MDR1 and LXRɑ/β. For patients with ovarian cancer, high cholesterol level in malignant ascites correlated with short RFS.
conclusionsHigh cholesterol in malignant ascites contributes to poor prognosis in ovarian cancer patients, partly by contributing to multidrug resistance through upregulation of MDR1 via activation of LXRɑ/β.
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