Combined inhibition of STAT3 and HIF-1α for enhancement of chemosensitivity in the model of human laryngeal squamous cacinoma in nude mice.
- Author:
Xiuying LU
;
Xiaoming LI
;
Qi SONG
;
Xiuru MA
;
Lifeng JIA
- Publication Type:Journal Article
- MeSH:
Animals;
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;
Mice, Nude;
Neoplasms, Experimental;
drug therapy;
metabolism;
STAT3 Transcription Factor;
genetics;
metabolism;
Tyrphostins;
pharmacology
- From:
Journal of Clinical Otorhinolaryngology Head and Neck Surgery
2016;30(4):314-318
- CountryChina
- Language:Chinese
-
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 of HIF-1α in group E was lower than that in group C and group D respectively, and there were significant difference respectively (t₁ = 6.140, t₂ = 3.667, P < 0.01). The expression level of p-STAT3 in group C was markedly lower compared with that in group B, and there were significant difference between them (t = 17.840, P < 0.01); There were no difference between the expression level of p-STAT3 in group D and that in group B (t = 0.038, 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.
