title: Triptolide Induces Apoptosis and Synergizes with Cisplatin in Cisplatin-Resistant HNE1/DDP Nasopharyngeal Cancer Cells.
abstract: The purpose of the study was to evaluate the anti-tumour effects of triptolide (TPL) and of the combination of TPL and cisplatin (DDP) in DDPresistant HNE1/DDP nasopharyngeal cancer (NPC) cells and to reveal the possible mechanisms. HNE1/ DDP cells were treated with TPL and/or DDP. Cell proliferation was examined by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT) assay and colony-forming assay; the combination index of the synergism between TPL and DDP was calculated. Cell morphological changes were observed under a microscope. Reactive oxygen species (ROS) and apoptosis rate were determined by flow cytometry. 5,5',6,6'-tetrachloro-1,1',3,3'-tetrethyl benzimidalyl carbocyanine iodide (JC-1) staining was used to determine mitochondrial membrane potential (MMP). Protein expression was analysed by Western blot, including Bax, caspase-9, Bcl-2, Mcl-1. TPL had an obvious anti-tumour effect and exhibited synergistic cytotoxicity with DDP on DDP-resistant HNE1/DDP cells. TPL induced HNE1/DDP cell apoptosis via inducing ROS generation. This effect was abolished by the inhibitor of ROS, N-acetyl-L-cysteine (NAC). TPL alone or combined with DDP could lower MMP significantly. Western blot showed that TPL alone or in combination with DDP increased expression of Bax and caspase-9, but reduced expression of Bcl-2 and Mcl-1. We conclude that TPL could induce cell apoptosis and synergize with DDP by regulating ROS generation and mitochondrial pathways in HNE1/DDP cells. This indicates that TPL may be effective in DDP-resistant NPC, either alone or combined with DDP.
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, the First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, the First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui, China.
authors.forename: J-J
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, the First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui, China.
authors.forename: Y-M
authors.initials: YM
authors.lastname: Sun
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, the First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Computational Chemical Genomics Screening Center, Pittsburgh, Pennsylvania, USA.
authors.forename: L-R
authors.initials: LR
authors.lastname: Wang
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, the First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui, China.
authors.forename: J-C
authors.initials: JC
authors.lastname: Li
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, the First Affiliated Hospital of Bengbu Medical College, Bengbu Anhui, China.
authors.forename: H
authors.initials: H
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D004224:Diterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D005434:Flow Cytometry; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide; D002945:Cisplatin