Artesunate (ART), derived from a common traditional Chinese medicine, has beeen used an antimalarial for several years. In this study, the effect and mechanism of ART on anti-human cervical cancer cells was examined. The level of prostaglandin E2 (PGE2 ) and the population of CD4+CD25+Foxp3 regulatory T cells (Treg) in peripheral blood were detected by flow cytometry. In vivo antitumor activity was investigated in mice with cervical cancer by the subcutaneous injection of various concentrations of ART. The concentrations of PGE2 in the supernatants of CaSki cells were measured using an ELISA kit. Cyclooxygenase-2 (COX-2) and Foxp3 expression were determined using quantitative polymerase chain reaction (qPCR) and western blot analysis. The effect of ART on the viability of CaSki and Hela cells was evaluated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. It was identified that the level of PGE2 and the population of CD4+CD25+Foxp3 Treg cells in the peripheral blood were significantly higher in cervical cancer patients and mice with cervical cancer. ART was capable of inhibiting orthotopic tumor growth, which correlated with a decrease in the level of PGE2 and the percentage of Treg cells in mice with cervical cancer. Furthermore, ART decreased COX-2 expression and the production of PGE2 in CaSki and Hela cells. Notably, the supernatants of CaSki cells treated with ART lowered the expression of Foxp3 in Jurkat T cells, which was capable of being reversed by exogenous PGE2 . Our data revealed that ART may elicit an anti-tumor effect against cervical cancer by inhibition of PGE2 production in CaSki and Hela cells, which resulted in the decrease of Foxp3 expression in T cells. Therefore, ART may be an effective drug for immunotherapy of cervical cancer.
Abstract:The loading and removal efficiency of 16 US EPA polycyclic aromatic hydrocarbons (PAHs) were examined in an inverted A 2 /O wastewater treatment plant (WWTP) located in an urban area in China. The total PAH concentrations were 554.3 to 723.2 ng/L in the influent and 189.6 to 262.7 ng/L in the effluent. The removal efficiencies of ∑PAHs in the dissolved phase ranged from 63 to 69%, with the highest observed in naphthalene (80% removal). Concentration and distribution of PAHs revealed that the higher molecular weight PAHs became more concentrated with treatment in both the dissolved phase and the dewatered sludge. The sharpest reduction was observed during the pretreatment and the biological phase. Noncarcinogenic risk, carcinogenic risk, and total health risk of PAHs found in the effluent and sewage sludge were also assessed. The effluent BaP toxic equivalent quantities (TEQ BaP ) were above, or far above, standards in countries. The potential toxicities of PAHs in sewage effluent were approximately 10 to 15 times higher than the acceptable risk level in China. The health risk associated with the sewage sludge also exceeded international recommended levels and was mainly contributed from seven carcinogenic PAHs. Given that WWTP effluent is a major PAH contributor to surface water bodies in China and better reduction efficiencies are achievable, the present study highlights the possibility of utilizing WWTPs for restoring water quality in riverine and coastal regions heavily impacted by PAHs contamination.
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