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Aims. We here investigated whether the combination of simvastatin and irinotecan could induce the synergistic effect on colon cancer cells with or without resistance to irinotecan. Methods. We investigated cell proliferation assay and assessed cell death detection ELISA and caspase-3 activity assay of various concentrations of simvastatin and irinotecan to evaluate the efficacy of drug combination on colon cancer cells with or without irinotecan resistance. Results. The IC50 values of simvastatin alone and irinotecan alone were 115.4 ± 0.14 μM (r = 0.98) and 62.5 ± 0.18 μM (r = 0.98) in HT-29 cells without resistance to irinotecan. The IC50 values of these two drugs were 221.9 ± 0.22 μM (r = 0.98) and 195.9 ± 0.16 μM (r = 0.99), respectively, in HT-29 cell with resistance to irinotecan. The results of combinations of the various concentrations of two drugs showed that combined treatment with irinotecan and simvastatin more efficiently suppressed cell proliferation of HT-29 cells even with resistance to irinotecan as well as without resistance. Furthermore, the combination of simvastatin and irinotecan at 2 : 1 molar ratio showed the best synergistic interaction. Conclusion. Simvastatin could act synergistically with irinotecan to overcome irinotecan resistance of colon cancer.
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http://dx.doi.org/10.1155/2016/7891374 | DOI Listing |
J Neurooncol
September 2025
Department of Neurology, University of Virginia School of Medicine, Charlottesville, VA, 22903, USA.
Purpose: This study investigates the synergistic therapeutic potential of a novel combination of the repurposed drug simvastatin with irinotecan chemotherapy towards glioblastoma (GBM) and the underlying molecular mechanisms.
Methods: In vitro efficacy of simvastatin and irinotecan alone and in combination against diverse GBM lines (U251MG, G34, SB28) was assessed using mechanistically distinct cell viability assays. RNA-Sequencing was performed to uncover the top pathways and genes affected by these drugs, followed by validation of promising pathways (TGF-β signaling and cell death) using targeted phosphoproteomics and in vitro genetic manipulation and functional assays.
Cancer Res Treat
July 2023
Center for Lung Cancer, National Cancer Center, Goyang, Korea.
Purpose: This study evaluated whether an addition of simvastatin to chemotherapy improves survival in ever-smokers with extensive disease (ED)-small cell lung cancer (SCLC).
Materials And Methods: This is an open-label randomized phase II study conducted in National Cancer Center (Goyang, Korea). Chemonaive patients with ED-SCLC, smoking history (≥ 100 cigarettes lifetime), and Eastern Cooperative Oncology Group performance status of ≤ 2 were eligible.
Saudi Pharm J
February 2018
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan.
Prostate cancer is one of the most common malignant tumors around the world. Hyperlipidemia is considered as one of the most important risk factors for the development of prostate cancer. Simvastatin is widely used for the treatment of hyperlipidemia and was previously shown to induce apoptosis in several cancer types including lung, colon, pancreas, breast, and prostate cancer.
View Article and Find Full Text PDFHum Genomics
May 2018
Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
Background: Variability in genes implicated in drug pharmacokinetics or drug response can modulate treatment efficacy or predispose to adverse drug reactions. Besides common genetic polymorphisms, recent sequencing projects revealed a plethora of rare genetic variants in genes encoding proteins involved in drug metabolism, transport, and response.
Results: To understand the global importance of rare pharmacogenetic gene variants, we mapped the variability in 208 pharmacogenes by analyzing exome sequencing data from 60,706 unrelated individuals and estimated the importance of rare and common genetic variants using a computational prediction framework optimized for pharmacogenetic assessments.
Gastroenterol Res Pract
March 2016
Division of Gastroenterology, Department of Internal Medicine, Dongtan Sacred Heart Hospital, Hallym University School of Medicine, Gyeonggi-do 18450, Republic of Korea.