Xihuang Pill inhibits the development of DMBA combined estrogen and progesterone induced breast precancerous lesions rats by PI3K/AKT/mTOR signaling pathway

Abstract Objective. To study the inhibitory effect of Xihuang Pill on the development of DMBA combined estrogen and progesterone induced breast precancerous lesions rats by PI3K/AKT/mTOR signaling pathway, and to explore the effect of Xihuang Pill in preventing and treating breast cancer. Method. Establishment of a rat model of breast precancerous lesion with DMBA combined estrogen and progesterone sequential induction for 10 weeks. Xihuang Pill was administered by gavage continuously for 4 weeks. Take rat breast tissue and stain with hematoxylin- eosin (HE). The pathomorphological changes were observed with light microscope; TUNEL staining to detect cell apoptosis in breast tissue; Western blot was used to detect the protein expression of P-PI3K, P-AKT (S473), P-AKT (T308), PTEN, P-Tuberin/TSC2, P-Tuberin (p-S939), p-mTOR, P-4E-BP1 in breast tissues. The qRT-PCR was used to detect the gene expression of PTEN mRNA and VEGF mRNA. Immunohistochemistry was used to detect the protein expression of P-S6, p-p70s6k and VEGF. Result. Compared with the disease model group, the low, middle and high dose Xihuang Pill groups could significantly reduce the degree of breast pathology, and the number of apoptosis of breast precancerous lesions cells increased with the increase of Xihuang Pill dose; The expression levels of P-PI3K, P-AKT (S473), P-AKT (T308), p-mTOR, P-4E-BP1, p-S6, p-p70S6K, VEGF protein and VEGF mRNA dropped with the increase of Xihuang Pill dose. The expression levels of PTEN, P-Tuberin/TSC2, P-Tuberin (p-S939) protein and PTEN mRNA elevated with the increase of Xihuang Pill dose. Conclusion. Xihuang Pill can promote the apoptosis of breast precancerous lesion cells and reduce the proliferation of vascular endothelial cells, and then inhibit the progression of breast precancerous lesions. Its mechanism probably associated with the regulation of PI3K/AKT/mTOR pathway related gene protein expression.