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
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has recently shown antitumor activity in various cancer cells including cancers of cervix, pancreas, prostate, liver and neuroblastoma. Numerous studies in vivo and in vitro indicate that DHA possesses unique antitumor features and appears to be a promising chemotherapeutic agents. Here we systematically review the advances in research of anticancer of dihydroartemisinin, as well as summarize the mechanisms of its inducing apoptosis,delay cell-cycle, inhibitory cell proliferation and downregulate angiogenesis.