PMID- 21348302 OWN - NLM STAT- MEDLINE DCOM- 20120919 LR - 20110224 IS - 0513-4870 (Print) IS - 0513-4870 (Linking) VI - 45 IP - 10 DP - 2010 Oct TI - [Synergistic effect and its possible mechanisms of lidamycin in combination with TRAIL in NSCLC]. PG - 1247-53 AB - This study is to investigate the effect and its possible mechanisms of lidamycin (LDM) combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in human non-small cell lung cancer (NSCLC) cells. MTT assay was used to determine the growth inhibition of the two ingredients on H460 cells. Apoptosis was examined by Annexin V-FITC/PI staining, flow cytometry assay and DNA-specific dye Hoechst 33342 staining. The level of TRAIL receptor and apoptosis-associated protein expression was detected by Western blotting analysis. The results showed that the IC50 value of LDM and TRAIL for H460 cells was 4.603 x 10(-10) mol x L(-1) and 915.3 ng x mL(-1) respectively, but the IC50 value of LDM was 3.064 x 10(-11) mol x L(-1) and 1.611 x 10(-11) mol x L(-1) when different concentrations of LDM was combined with 50 and 100 ng x mL(-1) TRAIL respectively. And the CDI value was less than 1. The apoptosis ratios also increased in the combination group relative to the single-agent treatment and the untreated control. Furthermore, the induction of the cleavage of PARP and the activation of Caspase-3 and Caspase-8 by the combination were more effective than LDM or TRAIL alone. At last, the level of death receptor 5 (DR5) expressions increased in a dose-dependent manner and time-related pattern. The data indicate that LDM inhibits the growth of H460 cells in vitro. DR5 induction contributes to enhancement of TRAIL-induced apoptosis by LDM in human non-small lung cancer cells. FAU - Yang, Jie AU - Yang J AD - Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. FAU - Chen, Shu-zhen AU - Chen SZ LA - chi PT - English Abstract PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Yao Xue Xue Bao JT - Yao xue xue bao = Acta pharmaceutica Sinica JID - 21710340R RN - 0 (Aminoglycosides) RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Enediynes) RN - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 120177-69-7 (C 1027) RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) RN - EC 3.4.22.- (CASP3 protein, human) RN - EC 3.4.22.- (CASP8 protein, human) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspase 8) SB - IM MH - Aminoglycosides/administration & dosage/*pharmacology MH - Antibiotics, Antineoplastic/administration & dosage/pharmacology MH - Apoptosis/*drug effects MH - Carcinoma, Non-Small-Cell Lung/metabolism/*pathology MH - Caspase 3/metabolism MH - Caspase 8/metabolism MH - Cell Line, Tumor MH - Cell Survival/drug effects MH - Dose-Response Relationship, Drug MH - Drug Synergism MH - Enediynes/administration & dosage/*pharmacology MH - Humans MH - Lung Neoplasms/metabolism/*pathology MH - Poly(ADP-ribose) Polymerases/metabolism MH - Receptors, TNF-Related Apoptosis-Inducing Ligand/*metabolism MH - TNF-Related Apoptosis-Inducing Ligand/administration & dosage/*pharmacology EDAT- 2011/02/26 06:00 MHDA- 2012/09/20 06:00 CRDT- 2011/02/26 06:00 PHST- 2011/02/26 06:00 [entrez] PHST- 2011/02/26 06:00 [pubmed] PHST- 2012/09/20 06:00 [medline] PST - ppublish SO - Yao Xue Xue Bao. 2010 Oct;45(10):1247-53.