ArticleScientific reports2021
Inhibition of checkpoint kinase 1 potentiates anticancer activity of gemcitabine in bladder cancer cells.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
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- RNA-Micelles as Self-Assembling Structures for Efficient Co-Delivery of Synergistic siRNA and Nucleoside Analogues to Treat CRC Lung Metastasis.Advanced functional materials · 2026Article
- CHK1 as a Metabolic and Immunological Regulator: Implications for Cancer Therapy.Oncology research · 2026Review
- SLC7A11-independent disulfidptosis induced by a two-pronged delivery strategy for bladder cancer chemotherapy and cisplatin-resistance reverse.Materials today. Bio · 2025Article
- Dual-source powered sea urchin-like nanomotors for intravesical photothermal therapy of bladder cancer.Journal of nanobiotechnology · 2025Article
- CHK1 inhibition overcomes gemcitabine resistance in non-small cell lung cancer cell A549.Molecular & cellular oncology · 2025Article
- Intravesical Tumor-Selective Mucoadhesive Hydrogel for Effective Chemotherapy In Murine Model.International journal of nanomedicine · 2025Article
- Dual-Spherical Multifunctional Nanomotors for Intravesical Bladder Cancer Therapy.International journal of nanomedicine · 2025Article
- Cucurbitacin IIb Extracted from Hemsleya penxianensis Induces Cell Cycle Arrest and Apoptosis in Bladder Cancer Cells by Regulating Cell Cycle Checkpoints and Mitochondrial Apoptotic Pathway.Plant foods for human nutrition (Dordrecht, Netherlands) · 2023Article
- Anti-Metastatic Effect of Pyruvate Dehydrogenase Kinase 4 Inhibition in Bladder Cancer via the ERK, SRC, and JNK Pathways.International journal of molecular sciences · 2022Article
- Nephrotoxicity in cancer treatment: An update.Advances in cancer research · 2022Article
- CDKN1A/p21American journal of cancer research · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Checkpoint kinases (CHKs) are involved in the DNA damage response in many cancer cells. CHK inhibitors have been used in clinical trials in combination with chemotherapeutics; however, their effect against bladder cancer remains unclear. Here, we investigated the efficacy of combining gemcitabine with MK-8776, a novel CHK1 inhibitor, in four bladder cancer cell lines. The effects of gemcitabine and MK-8776 on cell viability, clonogenicity, cell cycle, and apoptosis were examined alongside in vivo efficacy using murine xenograft tumor models. Combined treatment inhibited the viability and colony formation of bladder cancer cells compared to either single treatment. Although gemcitabine (10 nM) alone increased the cell number in S-phase, it increased the cell number in sub-G1 phase when combined with MK-8776 (0.5 µM). Combined treatment enhanced cleaved poly[ADP-ribose]-polymerase expression alongside the number of annexin-V-positive cells, indicating the induction of apoptosis. In vivo, administration of gemcitabine and MK-8776 was well tolerated and suppressed tumor growth. Mechanistically, the combined treatment elevated γH2A.X and suppressed Rad51 expression. Our study demonstrates that MK-8776 and gemcitabine combined induces apoptosis and suppresses proliferation in bladder cancer cells by inhibiting CHKs and DNA repair. Therefore, CHK1 inhibition combined with gemcitabine may be a potential treatment for bladder cancer.
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