RESUMEN
Objective To evaluate effects of acitretin on HaCaT cells cultured in hypoxic condition,and to preliminarily explore the possible therapeutic mechanisms of acitretin in psoriasis.Methods HaCaT cells were divided into several groups to be cultured in hypoxic condition with the presence of acitretin at concentrations of 10-5,10-6,10-7 and 10 8 mol/L respectively,with cells treated with dimethyl sulfoxide (DMSO) as DMSO control group and those receiving no treatment as blank control group.Cellular proliferative activity was evaluated by CCK-8 assay after 12-,24-and 36-hour hypoxic culture in vitro.The mRNA and protein expressions of hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) were determined by reverse transcription (RT)-PCR and Western-blot analysis,respectively,after 24-hour hypoxic culture.Results After 24-hour hypoxic culture,the cellular proliferation rate was inhibited by 13.31％ ± 1.15％,21.86％ ± 5.31％,32.05％ ± 2.99％ and 37.28％ ± 3.21％ in the 10 8-,10-7-,10-6-and 10-5-mol/L acitretin groups respectively.With the increase of culture duration and acitretin concentrations,the degree of inhibition on cellular proliferation increased gradually.Compared with the blank control group,the 10-5-mol/L acitretin group showed significantly decreased protein expression of HIF-1α (0.319 ± 0.180 vs.1.196 ± 0.088,P ＜0.05),as well as decreased mRNA and protein expressions of VEGF (mRNA:0.442 ± 0.090 vs.1.108 ± 0.073;protein:0.216 ± 0.066 vs.1.174 ± 0.186;both P ＜ 0.05).However,no significant difference was found in the mRNA expression of HIF-lα between the 10-5-mol/L acitretin group and blank control group.Conclusion Acitretin can suppress the in vitro proliferation of HaCaT cells cultured in hypoxic condition,and down-regulate the expressions of HIF-1α and VEGF proteins as well as VEGF mRNA.
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The current treatments of metastatic malignant melanoma include chemotherapy,targeted therapy,immune therapy and radiation therapy,but the treatment outcome is far from optimism.In order to im-prove the treatment efficiency,it is urgent to improve early diagnosis,and develop more effective treatment drugs and delivery systems.The application of nanotechnology in the diagnosis and therapy of melanoma can re-duce the resistance to the drugs,increase efficacy and reduce side effects.