ArticleBMC cancer2015
Topotecan synergizes with CHEK1 (CHK1) inhibitor to induce apoptosis in ovarian cancer cells.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Topotecan Synergizes with SP141 in the Management of Uveal Melanoma.bioRxiv : the preprint server for biology · 2026Article
- Learning drug synergy through environment-conditioned feature modulation.Bioinformatics (Oxford, England) · 2026Article
- A bioinformatics approach to identify potential biomarkers of high-grade ovarian cancer.Journal of the Turkish German Gynecological Association · 2026Article
- A First-in-Class Chemical-Induced Proximity System Achieves Dose-Dependent Control of Tumor Protein P53 Gene Activation in Preclinical Models of Gastric Cancer.ACS pharmacology & translational science · 2025Article
- Synergistic effect of a nonsteroidal anti-inflammatory drug in combination with topotecan on small cell lung cancer cells.Molecular biology reports · 2024Article
- DNA Damage Response Alterations in Ovarian Cancer: From Molecular Mechanisms to Therapeutic Opportunities.Cancers · 2023Review
- MiR-139-3p Targets CHEK1 Modulating DNA Repair and Cell Viability in Lung Squamous Carcinoma Cells.Molecular biotechnology · 2022Article
- Current Implications of microRNAs in Genome Stability and Stress Responses of Ovarian Cancer.Cancers · 2021Review
- Silencing Long Non-coding RNA LINC01224 Inhibits Hepatocellular Carcinoma Progression via MicroRNA-330-5p-Induced Inhibition of CHEK1.Molecular therapy. Nucleic acids · 2020Article
- Review
- Integrative genomics analysis of hub genes and their relationship with prognosis and signaling pathways in esophageal squamous cell carcinoma.Molecular medicine reports · 2019Article
- A temperature-sensitive phase-change hydrogel of topotecan achieves a long-term sustained antitumor effect on retinoblastoma cells.OncoTargets and therapy · 2019Article
- Long non-coding RNA LINC00485 acts as a microRNA-195 sponge to regulate the chemotherapy sensitivity of lung adenocarcinoma cells to cisplatin by regulating CHEK1.Cancer cell international · 2019Article
- DPY30 is required for the enhanced proliferation, motility and epithelial-mesenchymal transition of epithelial ovarian cancer cells.International journal of molecular medicine · 2018Article
- Cariprazine, A Dopamine D₂/D₃ Receptor Partial Agonist, Modulates ABCG2-Mediated Multidrug Resistance in Cancer.Cancers · 2018Article
- DUOXA1-mediated ROS production promotes cisplatin resistance by activating ATR-Chk1 pathway in ovarian cancer.Cancer letters · 2018Article
- miR-195 potentiates the efficacy of microtubule-targeting agents in non-small cell lung cancer.Cancer letters · 2018Article
- Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells.Oncology letters · 2018Article
- A lethal synergy induced by phellinus linteus and camptothecin11 in colon cancer cells.Oncotarget · 2018Article
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundTopotecan (TPT) is a therapeutic option for women with platinum-resistant or -refractory ovarian cancer. However, the dose-limiting toxicity of TPT is myelosuppression. This led us to seek a combination treatment to augment TPT anti-cancer activity in a cancer-targeted manner. Ovarian serous cancers, a major subtype, show dysregulated DNA repair pathway and often display a high level of CHEK1 (CHK1), a cell cycle regulator and DNA damage sensor. CHEK1 inhibitors are a novel approach to treatment, and have been used as single agents or in combination chemotherapy in many cancers.
methodsWe evaluated the cellular effects of TPT in a panel of high grade serous (HGS) and non-HGS ovarian cancer cells. We then determined IC50s of TPT in the absence and presence of CHEK1 inhibitor, PF477736. Synergism between TPT and PF477736 was calculated based on cellular viability assays. Cytotoxic effect of the combined treatment was compared with apoptotic activities by Caspase3/7 activity assay and Western blotting of cleaved-PARP1 and γH2AX.
resultsNon-HGS ovarian cancer cells were generally more sensitive to TPT treatment compared to HGS ovarian cancer cells. When combined with CHEK1 inhibitor, TPT potently and synergistically inhibited the proliferation of HGS ovarian cancer cells. This dramatic synergism in cellular toxicity was consistent with increases in markers of apoptosis.
conclusionsOur findings suggest that the addition of CHEK1 inhibitor increases the response of ovarian cancer cells to TPT. Furthermore, reduced dosages of both drugs achieved maximal cytotoxic effects by combining TPT with CHEK1 inhibitor. This strategy would potentially minimize side effects of the drugs for extended clinical benefit.
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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.