Combination of ionizing radiation and 2-thio-6-azauridine induces cell death in radioresistant triple negative breast cancer cells by downregulating CD151 expression.

Autor: Marni R; Cancer Biology Laboratory, Department of Life Sciences, GITAM (Deemed to Be University), GITAM School of Science, Visakhapatnam, 530045, A.P, India., Malla M; Department of Computer Science and Engineering, GITAM (Deemed to Be University), GITAM School of Technology, Visakhapatnam, 530045, A.P, India., Chakraborty A; Radiation Biology, Kolkata Centre, UGC-DAE-CSR, Kolkata, 700098, India., Voonna MK; Mahatma Gandhi Cancer Hospital & Research Institute, Visakhapatnam-, 530017, A.P, India., Bhattacharyya PS; Mahatma Gandhi Cancer Hospital & Research Institute, Visakhapatnam-, 530017, A.P, India., Kgk D; Mahatma Gandhi Cancer Hospital & Research Institute, Visakhapatnam-, 530017, A.P, India., Malla RR; Cancer Biology Laboratory, Department of Life Sciences, GITAM (Deemed to Be University), GITAM School of Science, Visakhapatnam, 530045, A.P, India. rmalla@gitam.edu.
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2024 Nov; Vol. 94 (5), pp. 685-706. Date of Electronic Publication: 2024 Aug 21.
DOI: 10.1007/s00280-024-04709-w
Abstrakt: Background: Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer and is frequently resistant to therapy, ultimately resulting in treatment failure. Clinical trials have demonstrated the potential of sensitizing radiation therapy (RT)-resistant TNBC through the combination of chemotherapy and RT. This study sought to explore the potential of CD151 as a therapy response marker in the co-treatment strategy involving ionizing radiation (IR) and the repurposed antiviral drug 2-Thio-6-azauridine (TAU) for sensitizing RT-resistant TNBC (TNBC/RR).
Methods: The investigation encompassed a variety of assessments, including viability using MTT and LDH assays, cell proliferation through BrdU incorporation and clonogenic assays, cell cycle analysis via flow cytometry, cell migration using wound scratch and Boyden chamber invasion assays, DNA damage assessment through γH2AX analysis, apoptosis evaluation through acridine-orange and ethidium bromide double staining assays, as well as caspase 3 activity measurement using a colorimetric assay. CD151 expression was examined through ELISA, flow cytometry and RT-qPCR.
Results: The results showed a significant reduction in TNBC/RR cell viability following co-treatment. Moreover, the co-treatment reduced cell migration, induced apoptosis, downregulated CD151 expression, and increased caspase 3 activity in TNBC/RR cells. Additionally, CD151 was predicted to serve as a therapy response marker for co-treatment with TAU and IR.
Conclusion: These findings suggest the potential of combination treatment with IR and TAU as a promising strategy to overcome RT resistance in TNBC. Furthermore, CD151 emerges as a valuable therapy response marker for chemoradiotherapy.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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