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Apoptosis Protein API-5 More Markedly Expressed in Chemoresistant TNBC

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11/25/2019
news-medical.net

NewsMedical.net

78 TNBC biopsies from patients with different responses to chemotherapy were analyzed for API-5 expression before any treatment.

Further studies on API-5 expression and inhibition were performed on patient-derived TNBC xenografts, one highly sensitive to chemotherapies and the other resistant to most tested drugs.

Clinical analyses of the 78 TNBC biopsies revealed that API-5 was more markedly expressed in endothelial cells before any treatment among patients with chemoresistant TNBC, and this was associated with greater micro-vessel density.

API-5 was originally identified as an anti-apoptotic protein in mouse fibroblasts and in human cervical carcinoma cell lines, in which API-5 significantly enhanced cell survival after serum deprivation or ultraviolet sensitization.

In vitro, a decrease in API-5 expression sensitized human cancer cell lines to apoptosis, and increased their sensitivity to anticancer drugs.

In human osteocarcinoma cells, API-5 promotes survival through the inhibition of an E2 promoter-binding factor, and the integrity of the leucine zipper domain is required for the anti-apoptotic functions of API-5.

Previous authors engineered an anti-API5 peptide composed of the LZ domain fused with the Antennapedia/Penetrating protein domain since the integrity of this domain is essential for the function of API-5. This LZ peptide is able to penetrate cells in vitro, and to cancel the API-5/acinus interaction.

In this pre-clinical study, the authors studied the expression of API-5 in patients with chemotherapy-resistant TNBC and the inhibition of API-5 in a resistant TNBC xenograft model.

The Benedetto/Bousquet Research Team concluded that Hypoxia is associated with drug resistance and they have previously demonstrated a link between cancer stem-cells, hypoxic niches and resistance to sunitinib in renal cell carcinoma.

In vivo, hypoxia has been shown to induce resistance to apoptosis in human cervical cancer cell lines through a selection of p53-mutated cells.

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