Artesunate exerts an anti-immunosuppressive effect on cervical cancer by inhibiting PGE2 production and Foxp3 expression.

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.

[Application of pragmatic clinical trials in clinical evaluation of Chinese medicine].

Since the evidence-based medicine (EBM) being evoked widely, to seek out the best evidence is becoming the pivotal step for the development of Chinese medicine (CM), and randomized controlled trial (RCT, at most times, it means explanatory clinical trial--ECT) has been accepted as the general golden standard for the evaluation of clinical intervention. However, it is noted that the traditional RCT (ECT) is unsuitable for the special characteristics of individual treatment in CM. The formation and development of CM theory is found on large amount of clinical experiences, and to evaluate its clinical efficacy and safety is the most primary task. Because the CM intervention measures are complex and individualized, the clinical effectiveness of CM is embodied as a complex system, which impacted greatly by the environment factors. It is deemed that the pragmatic clinical trial (PCT) has the character just fitting for the evaluation. The feasibility of PCT in CM clinical evaluation is discussed in this paper in order to raise a new issue for the evaluation of CM effectiveness.