Evodiamine Suppresses ABCG2 Mediated Drug Resistance by Inhibiting p50/p65 NF-κB Pathway in Colorectal Cancer.

Evodiamine (Evo), extracted from the Chinese herbal medicine Evodia rutaecarpa, has cytotoxic effects on different types of human cancer cells. However, its effects on drug resistance and their molecular mechanism and therapeutic target in colorectal cancer are not well understood. In the present study, we observed that Evo inhibited cell growth and induced apoptosis in adose-and time-dependent manner in HCT-116/L-OHP cells. Moreover, Evo treatment reduced Rhodamine 123 accumulation and ATPase activity in HCT-116/L-OHP cells, indicating that Evo decreased the efflux function in HCT-116/L-OHP cells. Interestingly, phosphorylation of NF-κB pathway, particularly p50/p65, was also inhibited by Evo treatment. Furthermore the effect of Evo in reversing drug resistance and suppressing phosphorylation of NF-κB pathway were attenuated after treatment with the NF-κB activator (LPS). Additionally, Evo inhibited the tumor growth in a colorectal MDR cancer xenograft model and down regulated p-NF-κB level in vivo. Our study provided the first direct evidence that Evo can attenuate multidrug resistance by blocking p-NF-κB signaling pathway in human colorectal cancer. Evo could be a potential candidate for cancer chemotherapy.

[Distribution Characteristics and Influencing Factors of Germanium in Soil in the Eastern Mountainous Area of the Nanyang Basin].

Based on the land quality geochemical survey results in the southwest cultivated area of Nanyang Basin, the content, spatial distribution, and enrichment characteristics of Ge in surface soil (0-20 cm) and deep soil (150-200 cm) in the eastern mountainous area of Nanyang Basin were studied, and the influencing factors of Ge in the surface soil were analyzed. The results showed that the average ω(Ge) in the surface soil and deep soil were 1.39 mg·kg-1 and 1.45 mg·kg-1, respectively. In the study area, 32.22% of surface soil and 12.77% of surface soil was rich in Ge, and the rich areas of the surface soil Ge were mainly distributed in the metamorphic rock and granite-dominant development areas. The optimal theoretical model of surface soil Ge variogram in the study area was a spherical model, and the nugget effect value was 0.434, indicating that surface soil Ge had moderate spatial correlation due to the joint influence of random factors and structural factors. The enrichment factor showed that 93.61% of Ge sites in the topsoil were mainly affected by natural factors, whereas 6.39% of Ge sites were significantly affected by human factors. The source of Ge in soil in the study area was mainly affected by the parent materials of soil formation, but the enrichment of Ge in surface soil was mainly affected by the Fe, Mn oxides, quartz, and pH in the soil.

Total extract of Xin Jia Xuan Bai Cheng Qi decoction inhibits pulmonary fibrosis via the TGF-ß/Smad signaling pathways in vivo and in vitro.

PURPOSE: Pulmonary fibrosis (PF) is a common clinical disease, which results in serious respiratory impairment. Xin Jia Xuan Bai Cheng Qi Decoction (XJXBCQ) is a traditional prescription commonly used in treating lung diseases. We investigate the effect of XJXBCQ against PF and its mechanism via the regulation of TGF-ß1/Smad in vitro and in vivo. MATERIALS AND METHODS: XJXBCQ was first extracted and probed for chemical characterization. An PF model in vitro and in vivo was established in rats and in MRC-5 cells. In bleomycin (BLM)-induced rats model, lung function such as peak expiratory flow (PEF), minute ventilation (MV) and hydroxyproline (HYP) were measured; histopathological changes of lung tissue and TGF-ß1 in peripheral blood of rats were detected. TGF-ß receptor, Smad2 and its phosphorylation expression were tested by Western blot assay in rats model. Then the effects of XJXBCQ on TGF-ß1/Smad signal pathway were assessed by Western blot analysis in vitro, and IL-17A and IL-25 levels were evaluated by ELISA in vivo. RESULTS: Our results showed that XJXBCQ significantly enhanced the lung functions, such as PEF, MV and HYP, by reducing the expression level of lung inflammatory cytokine and the content and fibrosis of lung collagen. Moreover, XJXBCQ effectively inhibited TGF-ß1, Smad2 and its phosphorylation expression, and the activation of Smad7 in vitro and in vivo. Furthermore, XJXBCQ had an inhibitory effect on the α-smooth muscle actin (α-SMA) and fibronectin (Fn) in vitro and downregulated IL-17A and IL-25 by inhibiting the activation of TGF-ß1/Smad signaling pathway in vitro and in vivo. Further, XJXBCQ effectively inhibitied ventilation volume and peak expiratory content remodeling and hydroxyproline content through inhibition of TGF-ßRⅡ, Smad2 and its phosphorylation expression, and activation of Smad7 in vivo. CONCLUSION: XJXBCQ extract had an anti-PF effect in vitro and in vivo, which could be attributed to the inhibition of the expression of p-Smad2 and increase in the expression of Smad7 by regulating the TGF-ß1/Smad activity.