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Apatinib increases anticancer potential of doxorubicin in breast cancer cells

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Abstract

Background

In recent years, drug resistance has become a most important challenge in chemotherapy of malignancies. Here, we investigated a novel approach to enhance therapeutic potential of doxorubicin (Dox as a common chemotherapeutic drug) by co-administration of apatinib (Apa as a monoclonal antibody) in breast cancer treatment.

Methods and results

Effects of Apa, Dox, and their combinations (Apa-Dox) were investigated on proliferation of MDA-MB-231 breast cancer cells by MTT assay. Moreover, migration and invasion of the treated and untreated control cancer cells were evaluated by scratch and transwell methods, respectively. Apoptosis percentage of the treated cancer cells was investigated by flow cytometry method. Finally, apoptosis-, metastasis-, and angiogenesis-related gene expression at mRNA and protein levels in the cancer cells were investigated by Real-Time PCR and western blotting methods, respectively. Our results indicated that treatments of cancer cells by Apa, Dox, and Apa-Dox significantly decrease proliferation, migration, and invasion of MDA-MB-231 breast cancer cells. Treatments of the breast cancer cells by Apa, Dox, and Apa-Dox significantly increase apoptosis percentage. We observed that anticancer effects of Apa, Dox, and Apa-Dox may due to modification of apoptosis-, metastasis-, and angiogenesis-related gene expression (at mRNA and protein level) in the breast cancer cells. However, anticancer potential of Apa-Dox combination was significantly more than Apa and Dox monotherapy.

Conclusion

We demonstrated that Apa significantly increases anticancer potential of Dox in MDA-MB-231 breast cells. However, further in-vitro, in-vivo, and clinical studies are required to confirm this result.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This article was adapted from the Ph.D. thesis of Elnaz Aghaei, where Dr. Hossein Soltanzadeh and Dr. Leila Kohan supervised, and Dr. Mohammad Heiat advised this project.

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Authors and Affiliations

  1. Department of Biology, Faculty of Science, Arsanjan Branch, Islamic Azad University, Arsanjan, Iran

    Elnaz Aghaei & Leila Kohan

  2. Department of Genetics, Bonab Branch, Islamic Azad University, Bonab, Iran

    Hossein Soltanzadeh

  3. Medicinal Plants Research Center, Maragheh University of Medical Sciences, Maragheh, Iran

    Hossein Soltanzadeh

  4. Baqiyatallah Research Center for Gastroenterology and Liver Disease (BRCGL), Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mohammad Heiat

Authors
  1. Elnaz Aghaei
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  2. Hossein Soltanzadeh
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  3. Leila Kohan
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  4. Mohammad Heiat
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Contributions

EA and HS designed this study, analyzed the data, prepared the figures and wrote original draft. LK and MH oversaw the study and revised the article. All Authors reviewed and approved the article.

Corresponding author

Correspondence to Hossein Soltanzadeh.

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Aghaei, E., Soltanzadeh, H., Kohan, L. et al. Apatinib increases anticancer potential of doxorubicin in breast cancer cells. Mol Biol Rep 50, 10137–10145 (2023). https://doi.org/10.1007/s11033-023-08860-0

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  • DOI: https://doi.org/10.1007/s11033-023-08860-0

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