Xihuang Pill Inhibits The Development of DMBA Combined With Oestrogen- And Progesterone-Induced Precancerous Breast lesions In Rats By The PI3K/AKT/mTOR Signaling Pathway

Abstract

Background:To study the inhibitory effect of Xihuang pill on the development of DMBA combined with oestrogen- and progesterone-induced breast precancerous lesions in rats by the 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 precancerous breast lesions with DMBA combined with oestrogen and progesterone sequential induction for 10 weeks. Xihuang pill was administered continuously by gavage for 4 weeks. Rat breast tissue was stained with haematoxylin-eosin (HE). The pathomorphological changes were observed with a light microscope. TUNEL staining was used to detect cell apoptosis in breast tissue. Western blotting 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, and P-4E-BP1 in breast tissues. 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 apoptotic precancerous breast lesion cells increased with increasing 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 increasing Xihuang pill dose. The expression levels of PTEN, P-tuberin/TSC2, P-tuberin (p-S939) protein and PTEN mRNA increased with increasing Xihuang pill dose. Conclusion:Xihuang pill can promote the apoptosis of precancerous breast lesion cells, reduce the proliferation of vascular endothelial cells, and then inhibit the progression of precancerous breast lesions. Its mechanism is probably associated with the regulation of the PI3K/AKT/mTOR pathway related protein expression.