Roles And Mechanisms Of Artemisinin In The Regulation Of Neuroblastoma Cell Proliferation

Neuroblastoma (Neuroblastoma, NB) evolved from the primitive neural crest cells. The sympathetic chain and the adrenal medulla are the most common primary sites. NB is a common childhood solid tumors, accounting for8%to10%of all childhood tumors. Different age, tumor location and degree of differentiation to their biological characteristics and clinical manifestations are very different. Some part of the NB patient could undergo partially spontaneous regression or into benign, but another part of the patient were very difficult to treat with poor prognosis. The treatment to NB patients are often at late stage, increasing the difficulty of treatment. The common treatment methods are the following:surgery, chemotherapy, radiotherapy, autologous hematopoietic stem cell transplantation, and cis retinoic acid treatment. The side effects of the above treatments may include:nausea, vomiting, hair loss, bone marrow suppression, weight loss, liver damage, kidney damage, heart damage, hearing loss, affecting fertility. Herbal treatment for NB:There is no similar records of NB in Chinese medicine, but can be attributed to the "Zheng Jia" category, reported in the literature that the use of the application of the insect drugs fire with fire. Artemisinin is the first successful anti-malarial drug developed by our country. It is the effective monomer separated from anti-malaria herbal Artemisia annua of China’s civil. The research began in the mid-1960s. Premier Zhou Enlai personally instructed and hundreds of scientists had been persistent in-depth study and the results achieved. It is one of a class of new drugs which was developed by our scientists’independent research and proved by the World Health Organization as the only truly effective drugs for the treatment of falciparum malaria. The main function of Artemisinin is to antimalarial including mouse malaria, monkey malaria and human malaria. In the early1980s, it is found that the efficacy of artemisinin includes anti-blood-sucking insects, gallbladder, expectorant, cough, asthma. Recent studies show that it has the anti-tumor effect. In this study, NB SHSY5Y cells were selected for the study. BrdU incorporation, agarose clonogenic experiments found that artemisinin treatment significantly inhibited cell proliferation and migration. In addition, artemisinin regulated the expression of cell cycle-related proteins, such as artemisinin can significantly increase p21, p27expression, and reduce Cyclin D1, cyclin E expression. Furthermore, we explored the molecular mechanisms of artemisinin regulation of cell proliferation, and for the first time found that artemisinin regulate cell growth and proliferation by activating AMP kinase (AMPK). AMPK inhibitor and AMPKa2siRNA can reverse the anti-tumor effect of artemisinin, which clearly show the artemisinin downstream signaling pathways and targeting mechanisms. Through the interpretation of these results, we preliminary show the effect of artemisinin against NB growth and proliferation and its underline molecular mechanisms, so as to provide a solid foundation for target discovery and screening of such tumors intervention, has important scientific significance and social significance.