title: [Thrichosanthin enhances cisplatin-induced laryngocarcinoma apoptosis through inhibiting transcription factor nuclear factor κB].
abstract: OBJECTIVE
  To investigate the combined effect of thrichosanthin (TCS) and cisplatin on Hep-2 and AMC-HN-8 cell proliferation.
  
  
  METHODS
  Hep-2 and AMC-HN-8 cells were treated with low (3 µg/ml) or high (10 µg/ml) concentration of cisplatin (10 µg/ml), TCS(5 µg/ml), or the combination TCS (5 µg/ml) and cisplatin (3 µg/ml), the cells no exposure to the drugs as control. Cell proliferation was detected by CCK-8. Toxicity of drugs to cells was evaluated by LDH assay. Flow cytometry was used to detect apoptosis. Western blot was performed to detect the expressions of JNK, phosphor-JNK, p38, phosphor-p38, NF-κB, inhibitor of κB (I-κB), and phospho-I-κB.
  
  
  RESULTS
  Compared with TCS (5 µg/ml) or cisplatin (3 µg/ml) alone, the combination of them had more significant inhibitory effect on the proliferation of Hep-2 and AMC-HN-8 cells (P < 0.01), but with no significant increase in cytotoxicity (P > 0.05). Western blot showed the expression of p-JNK/SAPK significantly increased in the cells treated with 5 µg/ml TCS for 48 hours, while the expression of NF-κB and phospho-I-κB increased in the cells treated with 3 µg/ml cisplatin. However in the cells treated with 5 µg/ml TCS combined with 3 µg/ml cisplatin, the expression of p-JNK stayed at a high level and the expressions of NF-κB and phospho-I-κB decreased dramatically compared to the cells treated with 3 µg/ml cisplatin alone.
  
  
  CONCLUSIONS
  TCS could enhance cisplatin-induced apoptosis in Hep-2 and AMC-HN-8, at least in part, by inhibiting the NF-κB signaling pathway and activating JNK/SAPK signaling pathway and thus strengthening the antitumor effects of cisplatin, which highlights the possibility of combined application of TCS and cisplatin in the treatment of laryngeal carcinoma.
authors.affiliation: Department of Otorhinolaryngology Head and Neck Surgery, Eye Ear Nose and Throat Hospital of Fudan University, Shanghai 200031, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Zhang
authors.forename: Li-ming
authors.initials: LM
authors.lastname: Lu
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Tao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D006801:Humans; D007822:Laryngeal Neoplasms / Q000188:drug therapy*; D020935:MAP Kinase Signaling System / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D014157:Transcription Factors; D002945:Cisplatin