ArticleInternational journal of molecular sciences2020
Combined Poziotinib with Manidipine Treatment Suppresses Ovarian Cancer Stem-Cell Proliferation and Stemness.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Calcium channels as pharmacological targets for cancer therapy.Clinical and experimental medicine · 2025Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Causal relationship between thyroid dysfunction and ovarian cancer: a two-sample Mendelian randomization study.BMC cancer · 2024Article
- The Role of Cancer Stem Cell Markers in Ovarian Cancer.Cancers · 2023Review
- Ion Channels and Personalized Medicine in Gynecological Cancers.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Targeting ovarian cancer stem cells: a new way out.Stem cell research & therapy · 2023Review
- "DEPHENCE" system-a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer-a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies.Frontiers in oncology · 2023Review
- Drug Repurposing to Enhance Antitumor Response to PD-1/PD-L1 Immune Checkpoint Inhibitors.Cancers · 2022Review
- A Review of HER4 (ErbB4) Kinase, Its Impact on Cancer, and Its Inhibitors.Molecules (Basel, Switzerland) · 2021Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy in women worldwide, with an overall 5 year survival rate below 30%. The low survival rate is associated with the persistence of cancer stem cells (CSCs) after chemotherapy. Therefore, CSC-targeting strategies are required for successful EOC treatment. Pan-human epidermal growth factor receptor 4 (HER4) and L-type calcium channels are highly expressed in ovarian CSCs, and treatment with the pan-HER inhibitor poziotinib or calcium channel blockers (CCBs) selectively inhibits the growth of ovarian CSCs via distinct molecular mechanisms. In this study, we tested the hypothesis that combination treatment with poziotinib and CCBs can synergistically inhibit the growth of ovarian CSCs. Combined treatment with poziotinib and manidipine (an L-type CCB) synergistically suppressed ovarian CSC sphere formation and viability compared with either drug alone. Moreover, combination treatment synergistically reduced the expression of stemness markers, including CD133, KLF4, and NANOG, and stemness-related signaling molecules, such as phospho-STAT5, phospho-AKT, phospho-ERK, and Wnt/β-catenin. Moreover, poziotinib with manidipine dramatically induced apoptosis in ovarian CSCs. Our results suggest that the combinatorial use of poziotinib with a CCB can effectively inhibit ovarian CSC survival and function.
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