RESUMEN

In this study, the pharmacokinetic properties and stability of isoliquiritigenin (ILQ) in microsomes were evaluated. The data showed ILQ administrated by i.h had high absorption degree (absolute bioavailability> 90%), and strong elimination ability (average t1/2≈ 67 min). ILQ in rat tissues could reach peak at 0.25 h, and be detected in almost all tissues. In vitro, stability of ILQ in four species liver microsomes were rat > beagle dog > monkey > human > mouse. On the basis of pharmacokinetic (PK) profiles, mechanism of ILQ against S180 was explored. ILQ could not inhibit S180 growth directly in vitro. However, ILQ extremely prohibited S180 tumor volume in vivo. And when TNF-α in NK cells was knocked down by siRNA, ILQ had no inhibiting effect on S180 tumor. ILQ enhanced TNF-α expression in NK cells by FCM detection. Autophagy-associated proteins LC3-II, Beclin-1, ATG-7 were elevated in S180 cells co-cultured with ILQ treating NK cells. When TNF-α was knocked down by siRNA, ILQ could not induce autophagy in S180 tumors. In the NK cells of osteosarcoma patients, TNF-α was negatively correlated with GSK-3ß by ELISA detection. ILQ could inhibit GSK-3ß expression and further increased p65 and c-Rel expression in NK cells. When GSK-3ß was knocked down by siRNA, ILQ did not affect p65 and c-Rel expression. ILQ directly inhibited GSK-3ß and then activated the NF-κB pathway to enhance TNF-α expression in NK cells, which could induce autophagy in sarcomas. The present study supplied a new mechanism for ILQ against tumors.

Asunto(s)

Autofagia/efectos de los fármacos , Chalconas/farmacología , Glycyrrhiza uralensis/química , Osteosarcoma/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Animales , Línea Celular Tumoral , Chalconas/uso terapéutico , Perros , Ensayos de Selección de Medicamentos Antitumorales , Femenino , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Haplorrinos , Humanos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Microsomas Hepáticos/efectos de los fármacos , Proteínas Asociadas a Microtúbulos/metabolismo , Osteosarcoma/sangre , Osteosarcoma/patología , Cultivo Primario de Células , Ratas , Ratas Wistar , Distribución Tisular , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Objective To investigate the long term clinical effect of unilateral and bilateral percutaneous vertebroplasty(PVP) on the treatment of single segment osteoporotic vertebral compression fractures (OVCFs).Methods A total of 95 patients with OVCFs were retrospectively investigated.Each patient completed Visual Assessment Score(VAS) and Short Form-36 (SF-36) questionnaires preoperatively and follow-up to the endpoints postoperatively to assess the long term effect of unilateral and bilateral PVP.Patients underwent unilateral PVP (44 cases),whereas others underwent bilateral PVP (51 cases).Results VAS of immediate postoperative score (2.69 ± 0.55),(2.50 ± 0.39) and the last follow-up score (2.63 ± 0.46),(2.48 ± 0.32) in both techniques of PVP were significantly lower than the preoperative score (7.56 ± 0.73),(7.45 ± 0.54) (t =1.895,1.801,all P ＜ 0.01).However,VAS score at each time point in the unilateral PVP and bilateral PVP showed no significant difference (P ＞ 0.05).The last follow-up SF-36 scores (84.92±2.88),(86.71 t 2.73) in unilateral PVP and bilateral PVP were significantly higher than the preoperative score (58.35 ± 2.69),(57.93 ± 2.45) (P ＜ 0.01).But each time point of the SF-36 scores in both groups showed no significant difference (P ＞ 0.05).Unilateral percutaneous vertebroplasty showed some advantages on operation time,radiation exposure and usage of bone cement.Meanwhile,the bone cement leakage and recurrence of OVCFs on the adjacent segment in the two groups presented no significance.Conclusion Both unilateraland bilateral PVP could benefit the long term outcome of OVCFs,with regard to the significant advantage of unilateral PVP on operation time,radiation exposure and usage of bone cement.

RESUMEN

10.3969/j.issn.2095-4344.2013.25.001