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

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.