# Ilex latifolia Improves the Anti-Tumor Effectiveness of Rapamycin Against Breast Cancer In Vitro and In Vivo

## TL;DR

This study shows that combining Ilex latifolia with rapamycin improves breast cancer treatment by reducing side effects and enhancing anti-tumor effects.

## Contribution

The novel finding is that Ilex latifolia synergizes with low-dose rapamycin to enhance anti-tumor efficacy while reducing metabolic side effects.

## Key findings

- Ilex latifolia combined with low-dose rapamycin synergistically inhibited tumor proliferation and induced apoptosis in breast cancer cells.
- In vivo, Ilex latifolia reduced rapamycin-induced lipid disturbances and tumor growth while enhancing apoptosis and reducing inflammation.
- Ilex latifolia shows promise as a dietary adjunct to improve the safety and effectiveness of rapamycin in breast cancer treatment.

## Abstract

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Although the mTOR inhibitor rapamycin exhibits notable anti-tumor activity, its clinical application is limited by metabolic side effects, particularly dyslipidemia. This study aimed to investigate the potential of Ilex latifolia (I. latifolia, large-leaf kudingcha), a traditional Chinese tea known for its lipid-lowering properties, to enhance the therapeutic efficacy of rapamycin in breast cancer. The combined effects of I. latifolia and low-dose rapamycin on tumor cell proliferation, cell cycle progression, apoptosis, and inflammation were assessed in four breast cancer cell lines and a murine breast cancer model. While low-dose I. latifolia alone exhibited limited anti-tumor activity, its combination with low-dose rapamycin synergistically inhibited tumor proliferation, induced cell cycle arrest, promoted apoptosis, and reduced inflammation in vitro. In vivo, dietary supplementation with I. latifolia mitigated rapamycin-induced lipid disturbances, reduced tumor growth, enhanced apoptosis, and alleviated inflammation in tumor tissues. These findings highlight I. latifolia as a promising dietary adjunct to rapamycin, providing a safer and more effective combinatorial strategy for breast cancer treatment.