RESUMO
Primary effusion lymphoma (PEL) is an aggressive B-cell malignancy without effective treatment, and caused by the infection of Kaposi's sarcoma-associated herpesvirus (KSHV), predominantly in its latent form. Previously we showed that the SUMO2-interacting motif within the viral latency-associated nuclear antigen (LANASIM) is essential for establishment and maintenance of KSHV latency. Here, we developed a luciferase based live-cell reporter system to screen inhibitors selectively targeting the interaction between LANASIM and SUMO2. Cambogin, a bioactive natural product isolated from the Garcinia genus (a traditional herbal medicine used for cancer treatment), was obtained from the reporter system screening to efficiently inhibit the association of SUMO2 with LANASIM, in turn reducing the viral episome DNA copy number for establishment and maintenance of KSHV latent infection at a low concentration (nM). Importantly, Cambogin treatments not only specifically inhibited proliferation of KSHV-latently infected cells in vitro, but also induced regression of PEL tumors in a xenograft mouse model. This study has identified Cambogin as a novel therapeutic agent for treating PEL as well as eliminating persistent infection of oncogenic herpesvirus.
Assuntos
Antineoplásicos/farmacologia , Linfoma de Efusão Primária/virologia , Terpenos/farmacologia , Latência Viral/efeitos dos fármacos , Animais , Antígenos Virais/efeitos dos fármacos , Antígenos Virais/metabolismo , Células HEK293 , Infecções por Herpesviridae/metabolismo , Herpesvirus Humano 8 , Humanos , Camundongos , Proteínas Nucleares/efeitos dos fármacos , Proteínas Nucleares/metabolismo , Extratos Vegetais/farmacologia , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/efeitos dos fármacos , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The study combined activated carbon with a rotating biological contactor. The activated carbon adsorption experiments were conducted and the biofilm was formed by using the river water directly. The effects of different hydraulic retention times on the removal of NH4+-N, TP, and permanganate index and on the biofilm properties were investigated at the optimum rotational speed of the disc. Experimental results are as follows. The Freundlich isotherm showed that activated carbon had better adsorption properties for NH4+-N, TP, and permanganate index in water.When the disk speed was 3 r·min-1, the removal efficiency was the best, and the removal rates of NH4+-N, TP and permanganate index were the best at 86.05%, 81.28%, and 77.09%, respectively. In addition, there was a significant linear correlation between the hydraulic retention time and the removal of NH4+-N and TP (R2>0.9), respectively. The removal rates of NH4+-N and TP at different hydraulic retention times were significantly different (P<0.05), but the permanganate index was not (P>0.05).Hydraulic retention time had effects on the biofilm activity, protein and polysaccharide contents,and the three-dimensional fluorescence peaks of S-EPS, LB-EPS, and TB-EPS of the biofilm.