ABSTRACT
OBJECTIVE@#To investigate the effects of combined inhibition of signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor-1α (HIF-1α) in the enhancement of chemosensitivity of the model of human laryngeal squamous cacinoma in nude mice.@*METHOD@#Model nude mice were divided into six groups randomly: control group(A) , cisplatin group(B) , cisplatin and AG490 group(C) , cisplatin and HIF-1α⁻/⁻ group (D), cisplatin combined AG490 and HIF-1α⁻/⁻ group (E), HIF-1α⁻/⁻ group (F) (only in calculating tumor inhibition rate). 3mg/kg cisplatin was administered by peritoneal injection for 3 days. Then cisplatin and 10 mg/kg AG490 were administered every other day for 12 days. The expression of Ki67 and HIF-1α was detected by immunocytochemical method. Western blot was used to detect the expression of p-STAT3.@*RESULT@#The expression of HIF-1α in group C and group D were lower than that in group B, and there were significant difference respectively (t₁ = 2.782, t₂ = 3.873, P 0.05); The expression level of p-STAT3 in group E was significantly lower compared with that in group C and group D respectively (P < 0.01). Tumor inhibition rate of group E was higher than that in group B, group C , as well as group D respectively and there were significant difference respectively (t₁ = 5.509, P < 0.01; t₂ = 3.422, P < 0.05; t₃ = 2.718, P < 0.05 ). Ki67 index of group E was lower than that in group B, group C as well as group D respectively and there were significant difference respectively(t₁ = 8.307, P < 0.01; t₂ = 3.736, P < 0.05; t₃ = 4.524, P < 0.01).@*CONCLUSION@#Combined inhibition of STAT3 and HIF-1α could enhance chemo-sensitivity in the model of human laryngeal squamous cacinoma in nude mice.
Subject(s)
Animals , Mice , Antineoplastic Agents , Pharmacology , Carcinoma, Squamous Cell , Drug Therapy , Metabolism , Cisplatin , Pharmacology , Drug Resistance, Neoplasm , Hypoxia-Inducible Factor 1, alpha Subunit , Genetics , Metabolism , Ki-67 Antigen , Metabolism , Laryngeal Neoplasms , Drug Therapy , Metabolism , Mice, Nude , Neoplasms, Experimental , Drug Therapy , Metabolism , STAT3 Transcription Factor , Genetics , Metabolism , Tyrphostins , PharmacologyABSTRACT
OBJECTIVE@#To investigate the expression of X-chromosome-linked inhibitors of apoptosis (XIAP) XIAP in laryngeal squamous carcinomas and the relationship between the expression of XIAP and clinical biological behaviors.@*METHOD@#Paraffin-embedded tissue specimens used for this study were obtained from 50 patients with laryngeal squamous carcinomas. The patients had received neither chemotherapy nor radiation therapy before tumor resection. Using immunohistochemical staining for the paraffin sections (SP methods), we examine the expression of XIAP protein in laryngeal squamous carcinomas and normal laryngeal tissues, investigate the connection of the XIAP expression with the clinicopathological parameters.@*RESULT@#The expression of XIAP protein was observed mainly in the cytoplasm and nucleus. The staining color was dark brown. The expression of XIAP is remarkably higher in laryngeal squamous carcinomas than that in normal laryngeal tissue specimens. The statistical analysis revealed that in laryngeal squamous carcinomas XIAP expression had no relationship with the elements such as age, sex, smoking history, tumor site and lymph node metastases. However, there is significant correlation between XIAP expression and tumor clinical stage, T stage and pathological stage (P < 0.05).@*CONCLUSION@#XIAP is expressed higher in laryngeal squamous carcinomas than in normal laryngeal tissues. The level of XIAP expression is associated with tumor clinicopathological characteristics in laryngeal squamous carcinomas. While tumor growth and malignancy increased, the expression of XIAP was up-regulated in laryngeal squamous carcinomas. It may play a role of anti-apoptosis in the process of carcinogenesis and development in laryngeal squamous carcinomas.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Carcinoma, Squamous Cell , Metabolism , Pathology , Laryngeal Neoplasms , Metabolism , Pathology , Neoplasm Staging , X-Linked Inhibitor of Apoptosis Protein , MetabolismABSTRACT
OBJECTIVE To investigate the role of XIAP in cisplatin-induced apoptosis and its possible mechanism. METHODS Hep-2 cells were treated with different concentrations of cisplatin for different times. Using crystal violet assay, RT-PCR and flow cytometry (FCM), we investingated the rate of the cell apoptosis and the expression of XIAP protein and mRNA at different times after treating with different concentrations of cisplatin. RESULTS Hep-2 cells were adherent and in normal survival condition with very low apoptosis rate. After treating with cisplatin, the rate of inhibition, the expression of XIAP protein and the rate of apoptosis were remarkably different between different concentrations and times. The expression of XIAP protein was down regulated accompanied by the augmentation of the rate of Hep-2 cell apoptosis. The products of RT-PCR were analyzed, demonstrating that the XIAP mRNA was down regulated with the increased concentrations of cisplatin overtime. Correlation analysis showed the rate of inhibition and the rate of apoptosis were positively correlated with increased concentrations of cisplatin for different times, however, the expression of XIAP protein was negatively correlated. The expression of XIAP protein and the rate of apoptosis were conversely correlated. CONCLUSION The most important pathway that cisplatin induces cell death is apoptosis. The levels of expression of XIAP proteinand mRNA in Hep2 cells are time-and concentration-dependent after treating with cisplatin. Down-regulation of the XIAP protein expression to augment the rate of apoptosis is one of the mechanisms for the cisplatin tokill the carcinoma cells.