Abstract

GONZALEZ, Diana Mayorga; PARRA, Michael Ramírez  and  GUTIERREZ, Fabio A. Aristizábal. HIF decoy improve cytotoxic effects of two chemotherapeutic agents on MDA-MB-231. Rev. colomb. biotecnol [online]. 2020, vol.22, n.2, pp.6-17.  Epub Feb 08, 2021. ISSN 0123-3475.  https://doi.org/10.15446/rev.colomb.biote.v22n2.73114.

Oncogenic processes like uncontrollable proliferation, resistance to apoptosis, increases in angiogenic mechanisms and immune evasion are regulated by transcription factors such HIF-1. Therefore, this molecule is regarded as a potential therapeutic target. To explore this possibility, a HIF-1 α oligonucleotide decoy (ODN) was designed to evaluate its efficiency on both a mono-therapeutic scheme and a mixed treatment with two chemotherapeutic agents within an in vitro model of breast cancer. After confirming the target location with flow cytometry and immunofluorescence assays, that decoy was transfected over the MDA-MB-231 cell line. We established the HIF-1 α ODN, Cisplatin and Taxol IC-50 using Resazurin tests. Cell death mechanisms was evaluated with TUNEL. Finally, we obtained the combination index (IC) of each chemical agents with the ODN. This study showed that HIF-1 α ODN caused a cytotoxic effect (up to 90%) in MDA-MB-231 during 72 hours post treatment. That effect did not appear in either the assay controls nor in non-tumor cell cultures (FIBRO). This agent is highly selective towards tumor cells, activating pro-apoptotic mechanisms. Additionally, HIF-1 α ODN increases the tumorigenic action of Cisplatin and Taxol on the cell line, due to an additive effect. For these reasons, HIF-1 α ODN has potential antitumor selective activity, decreasing cell proliferation, inducing apoptosis, and optimizing, in a synergistic manner, the efficacy of wide spectrum chemotherapeutic compounds when it used in a combined treatment.

Keywords : Cancer; hypoxia; cell proliferation; apoptosis; synergy.

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