title: [Synergistic effect and its possible mechanisms of lidamycin in combination with TRAIL in NSCLC].
abstract: 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.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yang
authors.forename: Shu-zhen
authors.initials: SZ
authors.lastname: Chen
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D053281:Enediynes / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C058024:C 1027; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8