Background: Prolactinoma is the most common hormone-secreting pituitary adenoma. Dopamine receptor agonists (DAs) are effective in reducing prolactin levels and tumor mass, but some prolactinoma patients are resistant to DAs. Treating patients with DA-resistant prolactinoma is challenging. In this study, we examined the anti-prolactinoma effect of artesunate (ART), a potential new treatment option for prolactinoma, and its mechanism of action.Methods: Cell Counting Kit-8 (CCK8) and flow cytometry were used to detect the effect of ART on the proliferation, cycle, and apoptosis of rat pituitary adenoma cell line MMQ. The subcellular localization of ART was observed using confocal fluorescence microscopy. The JC-1 mitochondrial membrane potential (MMP) detection and Seahorse assays were used to detect the effect of ART on mitochondrial function.Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were used to detect the effect of ART on the expression of prolactin (PRL) and apoptosis-related proteins. A mouse xenograft model of prolactinoma was used to detect the inhibitory effect of ART on MMQ in vivo.Results: ART specifically inhibited MMQ proliferation and PRL synthesis, induced G0/G1 phase arrest and apoptosis in vitro. ART accumulated in the mitochondria of MMQ cells, inhibiting mitochondrial respiratory function and mediating apoptosis through the mitochondrial pathway. ART also inhibited proliferation and activated the apoptosis of MMQ cells in vivo.Conclusions: ART has a strong inhibitory effect on prolactinoma both in vitro and in vivo, and its effects rely on high MMP to inhibit mitochondrial metabolism and induce apoptosis. Our results provide evidence for ART as a candidate drug for the treatment of prolactinoma.
Abstract. The aim of this study was to investigate the effects of diagnostic ultrasound on chorionic villi during early pregnancy in rats through the examination of heat shock protein 70 (HSP70) expression and apoptosis in chorionic villi. Using TUNEL, RT-PCR, western blot analysis and immunohistochemistry, the extent of apoptosis and the gene/ protein expression of HSP70, Bcl-2 and Bax was determined in the samples of the chorionic villus from the rats during early pregnancy. Compared with the unexposed group, there were clear signs that apoptosis had occurred in the villi exposed to ultrasound for 30 min. The expression of HSP70 and Bax in the villi gradually increased with the extended duration of exposure to ultrasound, whereas the expression of Bcl-2 gradually decreased. Bcl-2 expression did not differ significantly between the group exposed for 10 min and the group exposed for 20 min. Taken together, our data demonstrate that HSP70 may protect chorionic villi exposed to ultrasound by inhibiting apoptosis; however, its protective effects are limited over the extended duration of exposure to ultrasound. Thus, the prudent use of ultrasound during the early stages of pregnancy should be advocated.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.