# Enhancement of 3-MA in Paclitaxel Treatment of MDA-MB-231 Tumor-Bearing Nude Mice and Its Mechanisms

## TL;DR

This study shows that combining 3-MA with paclitaxel improves treatment of triple-negative breast cancer in mice by reducing tumor growth and enhancing cell death.

## Contribution

The study reveals that 3-MA enhances paclitaxel efficacy by inhibiting tumor cell autophagy and promoting apoptosis in TNBC.

## Key findings

- 3-MA reversed paclitaxel-induced autophagy and reduced tumor growth in mice.
- Combining 3-MA with paclitaxel increased apoptotic markers and reduced cell proliferation.
- The combination upregulated autophagy-related and apoptosis-related genes.

## Abstract

Triple-negative breast cancer (TNBC) poses significant challenges due to its high aggressiveness, poor prognosis, and the lack of effective targeted therapies. Paclitaxel (PTX) is a chemotherapeutic agent commonly used in the treatment of TNBC; however, its efficacy is often compromised by drug resistance mediated by autophagy. This study investigated the synergistic effects of the autophagy inhibitor 3-methyladenine (3-MA) and PTX in a TNBC nude mouse model. Monitoring tumor volume and employing HE staining, immunofluorescence, and transmission electron microscopy revealed that PTX monotherapy induced tumor autophagy, characterized by the accumulation of LC3B/VPS34 proteins and an increase in autophagosomes. However, the co-administration of 3-MA reversed this process, significantly decreasing the tumor growth rate. Immunofluorescence and qPCR demonstrated that the combination group had fewer Ki-67-positive cells and more Caspase-3-positive cells, along with upregulated expression of autophagy-related genes and Caspase-family apoptosis genes. Consequently, this study suggests that inhibiting autophagy with 3-MA disrupts the autophagy-mediated protective mechanism of tumor cells, promoting the activation of apoptotic signals and enhancing the antitumor activity of PTX. These findings may offer new molecular mechanistic insights and potential therapeutic strategies for overcoming PTX resistance in TNBC.