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Synergistic effect of a nonsteroidal anti-inflammatory drug in combination with topotecan on small cell lung cancer cells

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Abstract

Background

The topoisomerase I inhibitor topotecan (TPT) is used in the treatment of recurrent small cell lung cancer (SCLC). However, the drug has a limited success rate and causes distress to patients due to its side effects, such as hematologic toxicities, including anemia and thrombocytopenia. Due to these pharmacokinetic limitations and undesirable side effects of chemotherapeutic drugs, the development of combination therapies has gained popularity in SCLC. Meclofenamic acid (MA), a nonsteroidal anti-inflammatory drug, has demonstrated anticancer effects on various types of cancers through different mechanisms. This study aims to investigate the potential synergistic effects of MA and TPT on the small cell lung cancer cell line DMS114.

Methods and results

To assess the cytotoxic and apoptotic effects of the combined treatment of MA and TPT, trypan blue exclusion assay, Annexin V, acridine orange/propidium iodide staining, western blot, and cell cycle analysis were conducted. The results demonstrated that the combination of MA and TPT elicited synergistic effects by enhancing toxicity in DMS114 cells (P < 0.01) without causing toxicity in healthy epithelial lung cells MRC5. The strongest synergistic effect was observed when the cells were treated with 60 µM MA and 10 nM TPT for 48 h (CI = 0,751; DRI = 10,871).

Conclusion

This study, for the first time, furnishes compelling evidence that MA and TPT synergistically reduce cellular proliferation and induce apoptosis in SCLC cells. Combinations of these drugs holds promise as a potential therapeutic strategy to improve efficacy and reduce the side effects associated with TPT.

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Data availability

The datasets generated during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This study was supported by Kocaeli University Scientific Research Projects Coordination Unit under grant number 2019/035.

Funding

This work was supported by a grant from Kocaeli University (Grant No: 2019/035).

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Authors and Affiliations

  1. Faculty of Medicine, Department of Medical Biology, Kocaeli University, Kocaeli, Turkey

    Sevinc Yanar, Aylin Kanli, Murat Kasap & Merve Gulsen Bal Albayrak

  2. Faculty of Medicine, Department of Histology and Embryology, Sakarya University, Korucuk, Sakarya, 54290, Turkey

    Sevinc Yanar

  3. Faculty of Medicine, Department of Medical Biology, Sakarya University, Sakarya, Turkey

    Gamze Guney Eskiler & Asuman Deveci Ozkan

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Contributions

SY: Investigation, methodology, writing original draft. AK: Supervision, methodology. MK: Design of the work, reviewing and editing the manuscript. MGBA: Investigation, methodology. GGE: Methodology, interpretation of data. ADO: Investigation, methodology.

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Correspondence to Sevinc Yanar.

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Yanar, S., Kanli, A., Kasap, M. et al. Synergistic effect of a nonsteroidal anti-inflammatory drug in combination with topotecan on small cell lung cancer cells. Mol Biol Rep 51, 145 (2024). https://doi.org/10.1007/s11033-023-09055-3

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