期刊
ACTA PHARMACEUTICA SINICA B
卷 11, 期 11, 页码 3465-3480出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2021.05.027
关键词
SW33; GBM; G2; M phase; Apoptosis; Autophagy; mTOR; Anti-inflammation; Safety
资金
- Beijing Natural Science Foundation (China) [7212157]
- CAMS Innovation Fund for Medical Sciences (China) [2016-I2M-3-007]
- National Natural Science Foundation of China (China) [81703536, 81803584, 81703565]
- Science and Technology Major Projects for Major New Drugs Innovation and Development (China) [2018ZX09711001-005-025, 2018ZX09711001-012]
GBM is a deadly form of advanced glioma with no effective treatment currently available. Sinomenine derivative SW33 shows promising antitumor activity against GBM by regulating PI3K/AKT and AMPK signaling pathways, and inducing autophagy as well. SW33 appears to be a safe and effective drug for GBM treatment.
Glioblastoma multiforme (GBM) in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it. Studies of sinomenine, an alkaloid from the Chinese medicinal plant, Sinomenium acutum, showed that it had inhibitory effects on several kinds of cancer. Here, we synthesized a sinomenine derivative, sino-wcj-33 (SW33), tested it for antitumor activity on GBM and explored the underlying mechanism. SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells. It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis. Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body. SW33 also induced autophagy through the PI3K/AKT/mTOR and AMPK/mTOR pathways. Thus, SW33 appears to be a promising drug for treating GBM effectively and safely.
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