Exosomal miR-21 Derived from Paclitaxel-Resistant Breast Cancer Cells Promotes Chemoresistance in Breast Cancer via p53/PI3K/AKT/mTOR Signaling.

OBJECTIVE

To investigate whether exosomes derived from paclitaxel (PTX)-resistant breast cancer cells confer chemoresistance to parental cells and to explore the involvement of the p53/PI3K/AKT/mTOR signaling pathway in this process.

METHODS

Exosomes were isolated from PTX-sensitive and PTX-resistant breast cancer cells (MCF-7 and MDA-MB-231) and characterized by transmission electron microscopy, nanoparticle tracking analysis, and detection of exosomal markers. Bioinformatics analyses were performed to predict microRNAs potentially targeting TP53. Functional assays, including Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), quantitative real-time PCR (qRT-PCR), and Western blotting, were used to assess drug sensitivity, apoptosis, and pathway-related molecular changes in recipient cells. MicroRNA inhibition and p53 overexpression approaches were applied for mechanistic validation, and key experiments were conducted in multiple breast cancer cell models.

RESULTS

Exosomes derived from PTX-resistant cells significantly enhanced PTX resistance and attenuated apoptosis-related changes in recipient cells. Inhibition of exosomal miR-21 or restoration of p53 expression reversed these effects. Similar results were observed across different breast cancer subtypes.

CONCLUSION

These findings indicate that exosomal miR-21 derived from PTX-resistant breast cancer cells may contribute to chemoresistance, at least in part, by suppressing p53 and modulating PI3K/AKT/mTOR pathway activation.