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Article

In Vitro and In Vivo Effects of the Combination of Polypurine Reverse Hoogsteen Hairpins against HER-2 and Trastuzumab in Breast Cancer Cells

by
Ester López-Aguilar
1,
Patricia Fernández-Nogueira
2,3,
Gemma Fuster
3,4,5,6,
Neus Carbó
3,6,
Carlos J. Ciudad
1,7 and
Véronique Noé
1,7,*
1
Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona (UB), 08028 Barcelona, Spain
2
Unit of Biophysics and Bioengineering, Department of Biomedicine, School of Medicine and Health Sciences, Universitat de Barcelona (UB), 08028 Barcelona, Spain
3
Department of Biochemistry and Molecular Biomedicine, School of Biology, Universitat de Barcelona (UB), 08028 Barcelona, Spain
4
Tissue Repair and Regeneration Laboratory (TR2Lab), Institut de Recerca i Innovació en Ciències de la Vida i de la Salut a la Catalunya Central (IrisCC), 08500 Vic, Spain
5
Department of Biosciences, Faculty of Sciences, Technology and Engineering, Universitat de Vic-Universitat Central de Catalunya (UVic-UCC), 08500 Vic, Spain
6
Institute of Biomedicine, Universitat de Barcelona (IBUB), 08028 Barcelona, Spain
7
Institute of Nanoscience and Nanotechnology, Universitat de Barcelona (IN2UB), 08028 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2023, 24(8), 7073; https://doi.org/10.3390/ijms24087073
Submission received: 2 March 2023 / Revised: 28 March 2023 / Accepted: 7 April 2023 / Published: 11 April 2023
(This article belongs to the Special Issue Targeted Therapies and Molecular Methods in Cancer)
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Abstract

Therapeutic oligonucleotides are powerful tools for the inhibition of potential targets involved in cancer. We describe the effect of two Polypurine Reverse Hoogsteen (PPRH) hairpins directed against the ERBB2 gene, which is overexpressed in positive HER-2 breast tumors. The inhibition of their target was analyzed by cell viability and at the mRNA and protein levels. The combination of these specific PPRHs with trastuzumab was also explored in breast cancer cell lines, both in vitro and in vivo. PPRHs designed against two intronic sequences of the ERBB2 gene decreased the viability of SKBR-3 and MDA-MB-453 breast cancer cells. The decrease in cell viability was associated with a reduction in ERBB2 mRNA and protein levels. In combination with trastuzumab, PPRHs showed a synergic effect in vitro and reduced tumor growth in vivo. These results represent the preclinical proof of concept of PPRHs as a therapeutic tool for breast cancer.
Keywords: PPRH; HER-2; breast cancer; gene silencing; trastuzumab PPRH; HER-2; breast cancer; gene silencing; trastuzumab

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MDPI and ACS Style

López-Aguilar, E.; Fernández-Nogueira, P.; Fuster, G.; Carbó, N.; Ciudad, C.J.; Noé, V. In Vitro and In Vivo Effects of the Combination of Polypurine Reverse Hoogsteen Hairpins against HER-2 and Trastuzumab in Breast Cancer Cells. Int. J. Mol. Sci. 2023, 24, 7073. https://doi.org/10.3390/ijms24087073

AMA Style

López-Aguilar E, Fernández-Nogueira P, Fuster G, Carbó N, Ciudad CJ, Noé V. In Vitro and In Vivo Effects of the Combination of Polypurine Reverse Hoogsteen Hairpins against HER-2 and Trastuzumab in Breast Cancer Cells. International Journal of Molecular Sciences. 2023; 24(8):7073. https://doi.org/10.3390/ijms24087073

Chicago/Turabian Style

López-Aguilar, Ester, Patricia Fernández-Nogueira, Gemma Fuster, Neus Carbó, Carlos J. Ciudad, and Véronique Noé. 2023. "In Vitro and In Vivo Effects of the Combination of Polypurine Reverse Hoogsteen Hairpins against HER-2 and Trastuzumab in Breast Cancer Cells" International Journal of Molecular Sciences 24, no. 8: 7073. https://doi.org/10.3390/ijms24087073

APA Style

López-Aguilar, E., Fernández-Nogueira, P., Fuster, G., Carbó, N., Ciudad, C. J., & Noé, V. (2023). In Vitro and In Vivo Effects of the Combination of Polypurine Reverse Hoogsteen Hairpins against HER-2 and Trastuzumab in Breast Cancer Cells. International Journal of Molecular Sciences, 24(8), 7073. https://doi.org/10.3390/ijms24087073

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