PMID- 25371071 OWN - NLM STAT- MEDLINE DCOM- 20150615 LR - 20221207 IS - 1423-0380 (Electronic) IS - 1010-4283 (Linking) VI - 36 IP - 3 DP - 2015 Mar TI - Matrine inhibits the growth and induces apoptosis of osteosarcoma cells in vitro by inactivating the Akt pathway. PG - 1653-9 LID - 10.1007/s13277-014-2764-5 [doi] AB - Matrine, a natural product, has been demonstrated to be a promising chemotherapeutic drug for some cancers. Using flow cytometric analysis of the cell cycle and apoptosis, we found that matrine inhibited the proliferation and induced apoptosis in the human osteosarcoma (OS) cell lines MG63, HOS, U2OS, and SAOS2 in vitro in a dose-dependent manner. We therefore assessed the role of the serine/threonine kinase Akt in the regulation of matrine-mediated cell growth inhibition and apoptosis induction in human OS cell lines. After treatment for 48 h, matrine induced G0/G1-stage cell cycle arrest in MG63, U2OS, and SAOS2 cells associated with an increase in the expression of p27(Kip1) and a decrease in the expression of Akt, glycogen synthase kinase 3 (GSK3)-beta (Ser9), and cyclin D1. Furthermore, the pro-apoptotic factor Bax was upregulated. Overall, our findings suggest that matrine may be an effective anti-osteosarcoma drug due to its ability to inhibit proliferation and induce apoptosis in OS cells, possibly through the involvement of Akt signaling. FAU - Xu, Gong-Ping AU - Xu GP AD - Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, 148 Baojian Road, Harbin, 150081, China. FAU - Zhao, Wei AU - Zhao W FAU - Zhuang, Jin-Peng AU - Zhuang JP FAU - Zu, Jia-Ning AU - Zu JN FAU - Wang, Duan-Yang AU - Wang DY FAU - Han, Fei AU - Han F FAU - Zhang, Zhi-Peng AU - Zhang ZP FAU - Yan, Jing-Long AU - Yan JL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141105 PL - Netherlands TA - Tumour Biol JT - Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine JID - 8409922 RN - 0 (Alkaloids) RN - 0 (BAX protein, human) RN - 0 (CDKN1B protein, human) RN - 0 (Quinolizines) RN - 0 (bcl-2-Associated X Protein) RN - 136601-57-5 (Cyclin D1) RN - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27) RN - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.26 (Glycogen Synthase Kinase 3) RN - 0 (Matrines) SB - IM MH - Alkaloids/*pharmacology MH - Apoptosis/*drug effects MH - Bone Neoplasms/*drug therapy/metabolism/pathology MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Cyclin D1/metabolism MH - Cyclin-Dependent Kinase Inhibitor p27/metabolism MH - G1 Phase Cell Cycle Checkpoints/drug effects MH - Glycogen Synthase Kinase 3/metabolism MH - Glycogen Synthase Kinase 3 beta MH - Humans MH - Osteosarcoma/*drug therapy/metabolism/pathology MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Quinolizines/*pharmacology MH - Resting Phase, Cell Cycle/drug effects MH - Signal Transduction/*drug effects MH - bcl-2-Associated X Protein/metabolism MH - Matrines EDAT- 2014/11/06 06:00 MHDA- 2015/06/16 06:00 CRDT- 2014/11/06 06:00 PHST- 2014/08/10 00:00 [received] PHST- 2014/10/22 00:00 [accepted] PHST- 2014/11/06 06:00 [entrez] PHST- 2014/11/06 06:00 [pubmed] PHST- 2015/06/16 06:00 [medline] AID - 10.1007/s13277-014-2764-5 [doi] PST - ppublish SO - Tumour Biol. 2015 Mar;36(3):1653-9. doi: 10.1007/s13277-014-2764-5. Epub 2014 Nov 5.