PMID- 27464548 OWN - NLM STAT- MEDLINE DCOM- 20170324 LR - 20211203 IS - 0376-2491 (Print) IS - 0376-2491 (Linking) VI - 96 IP - 27 DP - 2016 Jul 19 TI - [A dual PI3K/mTOR inhibitor, PI-103, cooperates with TRAIL in laryngeal squamous carcinoma cells in vitro]. PG - 2187-91 LID - 10.3760/cma.j.issn.0376-2491.2016.27.017 [doi] AB - OBJECTIVE: To investigate the effects of a dual phosphoinosmde-3-kinase (PI3K)/ mammalian target of rapamycin (mTOR) inhibitor, PI-103, cooperating with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the laryngeal squamous carcinoma Hep-2 cells. METHODS: Hep-2 cells were divided into 7 groups: LY294002 group, Rapamycin group, PI-103 group, LY294002+ TRAIL group, Rapamycin+ TRAIL group, PI-103+ TRAIL group and control group.The cell cycle and apoptosis of Hep-2 cells were assessed by flow cytometry.For PI-103 group, PI-103+ TRAIL group and control group, migration and invasion ability were measured by transwell migration and invasion assay respectively.The expression of relative proteins in apoptosis and PI3K/AKT/mTOR signal pathway was examined by Western blotting. RESULTS: Combination of PI-103 and TRAIL could make cell cycle arrest at S phase (G1: 1.80%+/-0.30%; G2: 0.00), inhibit cell proliferation, and enhance apoptosis (66.78%+/-2.93%) (P<0.05). Combination of PI-103 and TRAIL could statistically decrease the migration and invasion number of Hep-2 cells (17.0+/-3.4, 18.4+/-5.4) than that of PI-103 group (41.2+/-3.8, 41.6+/-4.7). PI-103 could inhibit PI3K/AKT/mTOR signal pathway by decreasing the protein expression of p-AKT and p-4E-BP1.Comparing with the control group, the expression of cysteinyl aspartate specific proteinase (Caspase) 9, 8, 3 were increased while the expression of Cyclin D1, Cyclin E1, p-AKT, p-4E-BP1 were decreased in PI-103 and PI-103+ TRAIL group (P<0.05). CONCLUSION: Enhanced anti-tumor effects was observed by combination of PI-103 and TRAIL on laryngeal cancer cells in vitro and this combined administration might be a promising strategy for clinical treatment of laryngeal cancer. FAU - Gao, C L AU - Gao CL AD - Department of Otorhinolaryngology, Eye Ear Nose and Throat Hospital, Fudan University, Shanghai 200031, China. FAU - Li, K N AU - Li KN FAU - Zhou, L AU - Zhou L FAU - Tao, L AU - Tao L FAU - Zhang, M AU - Zhang M LA - chi PT - Journal Article PL - China TA - Zhonghua Yi Xue Za Zhi JT - Zhonghua yi xue za zhi JID - 7511141 RN - 0 (CCND1 protein, human) RN - 0 (CCNE1 protein, human) RN - 0 (Chromones) RN - 0 (Cyclin E) RN - 0 (Furans) RN - 0 (Morpholines) RN - 0 (Oncogene Proteins) RN - 0 (PI103) RN - 0 (Pyridines) RN - 0 (Pyrimidines) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 136601-57-5 (Cyclin D1) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - Apoptosis MH - Carcinoma, Squamous Cell MH - Cell Cycle MH - Cell Line, Tumor MH - Cell Proliferation MH - Chromones MH - Cyclin D1 MH - Cyclin E MH - Furans MH - Head and Neck Neoplasms MH - Humans MH - Laryngeal Neoplasms MH - Morpholines MH - Oncogene Proteins MH - Phosphatidylinositol 3-Kinases MH - Pyridines MH - Pyrimidines MH - *Signal Transduction MH - Squamous Cell Carcinoma of Head and Neck MH - TNF-Related Apoptosis-Inducing Ligand MH - TOR Serine-Threonine Kinases EDAT- 2016/07/29 06:00 MHDA- 2017/03/25 06:00 CRDT- 2016/07/29 06:00 PHST- 2016/07/29 06:00 [entrez] PHST- 2016/07/29 06:00 [pubmed] PHST- 2017/03/25 06:00 [medline] AID - 10.3760/cma.j.issn.0376-2491.2016.27.017 [doi] PST - ppublish SO - Zhonghua Yi Xue Za Zhi. 2016 Jul 19;96(27):2187-91. doi: 10.3760/cma.j.issn.0376-2491.2016.27.017.