The inhibitory effect of lenvatinib plus fluvastatin on liver transplantation tumor in mice and corresponding mechanism / 中国药理学通报

Aim To explore the inhibitory effect of lenvatinib plus fluvastatin on liver transplantation tumor in mice and the mechanism.Methods Mouse model of subcutaneous liver cancer was used.Single agent of lenvatinib, single agent of fluvastatin, a combination of lenvatinib and fluvastatin and control solvent were given to four groups of mice.Tumor volume was measured.Immunohistochemistry was used to examine proliferation of tumor cells.Tunel was employed to detect the cell apoptosis.qRT-PCR and immunohistochemistry were used to measure the expression of TLR4.Western blot was employed to determine β-catenin expression.Rescue experiment was done using human hepatoma cells cultured in vitro.Results Treatment with both lenvatinib and fluvastatin significantly suppressed tumor growth in nude mice.Combined treatment significantly decreased the expressions of PNCA and increased apoptosis in tumor cells.Mechanically combined treatment synergistically suppressed the mRNA and protein expression of TLR4 which further inhibited the expression of β-catenin in hepatoma cells.Conclusions A combination of lenvatinib and fluvastatin synergistically inhibits tumor growth and promotes tumor cell apoptosis.The combination treatment significantly inhibits TLR4/β-catenin signaling pathway.

[Relationship Between the Bacterial Abundance and Production with Environmental Factors in a Subtropical Karst Reservoir].

In recent years, the increasing scarcity of water resources and eutrophication of water have become more serious. Reservoirs that are far from big cities have become important sources of drinking water and were targets of research and protection. Therefore, the abundance and production of bacteria and their correlations with environmental factors were investigated in the Dalongdong Reservoir, Shanglin County, Guangxi Province, using Quantitative Real-time PCR technology and the 14C tracer technique. The Dalongdong Reservoir is a typical subtropical karst reservoir. The bacterial abundance of the surface water decreased from the upstream to the downstream along the water flow direction and then increases. The vertical distribution of the bacterial abundance at each sampling site shows a similar trend; it is the highest in the surface water and the lowest on the bottom. The correlation analysis results show that the temperature, pH, electrical conductivity, dissolved organic carbon (DOC), chlorophyll-a, dissolved oxygen (DO), and other environmental factors significantly correlate with the bacterial abundance, indicating that these parameters are the main factors limiting the bacterial abundance in this region. The bacterial production is positively correlated with the pH, DOC, and permanganate index; negatively correlated with the conductivity and DIC; and significantly positively correlated with DO. The principal component analyses (PCA) shows that the environmental factors affecting the bacterial abundance and bacterial production can be grouped into two PCAs. PCA1 includes the temperature, pH, electrical conductivity, DIC, DO, chlorophyll-a, DOC, and permanganate index and PCA2 includes TN and TP. The bacterial abundance and production in the Dalongdong Reservoir are affected by various environmental factors and photosynthetic bacteria are the important contributors to the production of organic carbon.