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Combination of resveratrol and BIBR1532 inhibits proliferation of colon cancer cells by repressing expression of LncRNAs

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Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide. The development of tumor drug resistance is observed in the treatment of CRC. Combinations of anticancer agents are attracting considerable interest in order to overcome drug resistance in CRC. This study aims to investigate the effect of resveratrol and BIBR1532, either alone or in combination, on the cell viability as well as on expression of long non-coding RNAs (LncRNAs) for HT-29 colon adenocarcinoma cells. The cytotoxic effects of resveratrol and BIBR1532 on HT-29 cells were determined using WST-1 test. Flow cytometry was used to determine apoptotic cell death after treatments. Real-Time PCR was used to identify expression of LncRNAs after treatments. LncExpDB and GEPIA2 were used to evaluate expression profiles of LncRNAs, whose expression levels were decreased in HT-29 cells after treatments, in normal tissues and colon adenocarcinoma tumors. IC50 concentrations of BIBR1532 and resveratrol were found to be 50.81 μM at 48 h and 86.23 μM at 72 h, respectively. Combination index value was 1.07617. BIBR1532, resveratrol, or their combination reduced the cell viability of HT-29 cells. CCAT1, CRNDE, HOTAIR, PCAT1, PVT1, SNHG16 were down-regulated after treatments. In silico analysis revealed that LncRNAs whose expression levels were decreased after treatments were associated with CRC. Resveratrol, BIBR1532, or their combination may have anti-proliferative effect on colorectal cancer cells through repressing expression of LncRNAs that are involved in progression of CRC.

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Data availability

The data presented in this study are available on request from the corresponding author.

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Acknowledgements

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Funding

This study was sponsored by Ege University Research Fund, Project No. TYL-2019-20515 (to Cigir Biray Avci).

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Author notes

  1. Bakiye Goker Bagca and Hasan Onur Caglar have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Biology, Medical Faculty, Ege University, 35100, Izmir, Turkey

    Selin Cesmeli, Neslihan Pinar Ozates, Cumhur Gunduz & Cigir Biray Avci

  2. Department of Medical Biology, Medical Faculty, Aydın Adnan Menderes University, 09010, Aydın, Turkey

    Bakiye Goker Bagca

  3. Department of Molecular Biology and Genetics, Science Faculty, Erzurum Technical University, 25250, Erzurum, Turkey

    Hasan Onur Caglar

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  1. Selin Cesmeli
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Contributions

Conceptualization: SC, BGB, HOC, NPO, CG; Methodology: SC, BGB, HOC, NPO; Formal analysis and investigation: SC, CG; Writing-original draft preparation: SC, HOC; Writing-review and editing: CBA; Supervision: CBA.

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Correspondence to Cigir Biray Avci.

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Cesmeli, S., Goker Bagca, B., Caglar, H.O. et al. Combination of resveratrol and BIBR1532 inhibits proliferation of colon cancer cells by repressing expression of LncRNAs. Med Oncol 39, 12 (2022). https://doi.org/10.1007/s12032-021-01611-w

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