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首页> 外文期刊>International journal of hyperthermia: The official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group >Radiofrequency ablation combined with liposomal quercetin to increase tumour destruction by modulation of heat shock protein production in a small animal model
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Radiofrequency ablation combined with liposomal quercetin to increase tumour destruction by modulation of heat shock protein production in a small animal model

机译：在小动物模型中，射频消融联合脂质体槲皮素可通过调节热激蛋白的产生来增加肿瘤破坏

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Purpose: To investigate the effect of heat shock protein (HSP) modulation on tumour coagulation by combining radiofrequency (RF) ablation with adjuvant liposomal quercetin and/or doxorubicin in a rat tumour model. Methods: Sixty R3230 breast adenocarcinoma tumours/animals were used in this IACUC-approved study. Initially, 60 tumours (n?=?6, each subgroup) were randomised into five groups: (1) RF alone, (2) intravenous (IV) liposomal quercetin alone (1?mg/kg), (3) IV liposomal quercetin followed 24?h later with RF, (4) RF followed 15?min later by IV liposomal doxorubicin (8?mg/kg), (5) IV liposomal quercetin 24?h before RF followed by IV liposomal doxorubicin 15?min post-ablation. Animals were sacrificed 4 or 24?h post-treatment and gross coagulation diameters were compared. Next, immunohistochemistry staining was performed for Hsp70 and cleaved caspase-3 expression. Comparisons were performed by using Student t-tests or ANOVA. Results: Combination RF-quercetin significantly increased coagulation size compared with either RF or liposomal quercetin alone (13.1?±?0.7?mm vs. 8.8?±?1.2?mm or 2.3?±?1.3?mm, respectively, P??0.001 for all comparisons). Triple therapy (quercetin-RF-doxorubicin) showed larger coagulation diameter (14.5?±?1.0?mm) at 24?h than quercetin-RF (P?=?0.016) or RF-doxorubicin (13.2?±?1.3?mm, P?=?0.042). Combination quercetin-RF decreased Hsp70 expression compared with RF alone at both 4?h (percentage of stained cells/hpf 22.4?±?13.9% vs. 38.8?±?16.1%, P??0.03) and 24?h (45.2?±?10.5% vs. 81.1?±?3.6%, P??0.001). Quercetin-RF increased cleaved caspase-3 expression at both 4?h (percentage of stained cells/hpf 50.7?±?13.4% vs. 41.9?±?15.1%, P??0.03) and 24?h (37.4?±?7.8% vs. 33.2?±?6.5%, P?=?0.045); with, triple therapy (quercetin-RF-doxorubicin) resulting in the highest levels of apoptosis (45.1?±?10.7%) at 24?h. Similar trends were observed for rim thickness. Conclusions: Suppression of HSP production using adjuvant liposomal quercetin can increase apoptosis and improve RF ablation-induced tumour destruction. Further increases in tumour coagulation can be seen including an additional anti-tumour adjuvant agent such as liposomal doxorubicin.
机译：目的：通过将射频消融与辅助脂质体槲皮素和/或阿霉素联合在大鼠肿瘤模型中研究热休克蛋白（HSP）调节对肿瘤凝结的影响。方法：在该IACUC批准的研究中使用了六十种R3230乳腺腺癌/动物。最初，将60个肿瘤（n？=？6，每个亚组）随机分为5组：（1）仅RF，（2）静脉内（IV）单独的脂质体槲皮素（1？mg / kg），（3）IV脂质体槲皮素其次是RF，24分钟后，（4）RF，15分钟后，静脉内脂质体阿霉素（8？mg / kg），（5）RF前24分钟，静脉内脂质体槲皮素，RF后24分钟，IV，脂质体阿霉素消融。处理后4或24小时处死动物，并比较总凝结直径。接下来，对Hsp70和切割的caspase-3表达进行免疫组织化学染色。通过使用学生t检验或ANOVA进行比较。结果：与单独使用RF或脂质体槲皮素相比，组合RF-槲皮素显着增加了凝血大小（分别为13.1？±？0.7？mm与8.8？±1.2？mm或2.3？±？1.3？mm，P ？所有比较均为0.001）。三联疗法（槲皮素-RF-阿霉素）在24？h时的凝结直径（14.5？±？1.0？mm）比槲皮素-RF（P？=？0.016）或RF-阿霉素（13.2？±？1.3？mm）更大， P≥0.042）。槲皮素-RF组合与单独RF相比在4？h（染色细胞/ hpf的百分比为22.4？±？13.9％与38.8？±？16.1％，P？<？0.03）和24？h（45.2h）下均降低了Hsp70表达。相对于81.1±3.6％，±10.5％，P ＜＜ 0.001）。槲皮素-RF在4？h（染色细胞百分比/ hpf的百分比为50.7？±？13.4％与41.9？±？15.1％，P？<？0.03）和24？h（37.4？± 7.83％对33.2％±6.5％，P ＝ 0.045）。三联疗法（槲皮素-RF-阿霉素）在24小时时可导致最高水平的细胞凋亡（45.1±±10.7％）。对于轮辋厚度观察到相似的趋势。结论：辅酶脂质体槲皮素抑制热休克蛋白的产生可以增加细胞凋亡并改善射频消融引起的肿瘤破坏。可以看到肿瘤凝结的进一步增加，包括另外的抗肿瘤佐剂，如脂质体阿霉素。

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