Combination radiofrequency (RF) ablation and IV liposomal heat shock protein suppression: reduced tumor growth and increased animal endpoint survival in a small animal tumor model.
Combination radiofrequency (RF) ablation and IV liposomal heat shock protein suppression: reduced tumor growth and increased animal endpoint survival in a small animal tumor model.
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DOI：
10.1016/j.jconrel.2011.12.031
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发表时间：
2012-06-10
期刊：
影响因子：
--
通讯作者：
Goldberg SN
中科院分区：
文献类型：
--
作者：
Yang W;Ahmed M;Tasawwar B;Levchenko T;Sawant RR;Torchilin V;Goldberg SN
在大鼠肿瘤模型中，研究IV脂质体槲皮素（一种已知的热休克蛋白下调剂）单独给药以及与脂质体多柔比星联合射频（RF）肿瘤消融术对肿瘤生长和终点生存率的影响。将孤立的皮下R3230乳腺癌肿瘤（1.3-1.5 cm）植入48只雌性Fischer大鼠中。最初，将32个肿瘤（n=8，每组）随机分为四个实验组：（a）单独的常规单极RF（70 ℃，5分钟），（B）单独的IV脂质体槲皮素（1 mg/kg），（c）IV脂质体槲皮素，24小时后用RF，和（d）不处理。接下来，将另外16个肿瘤随机分为两组（每组n=8），接受RF和脂质体多柔比星的组合（RF后15分钟，8 mg/kg），有或没有脂质体槲皮素。使用肿瘤直径3.0 cm作为定义的生存终点进行Kaplan-Meier生存分析。各组间的终点生存率和肿瘤倍增时间差异有高度显著性（P<0.001）。对照组的终点生存期为12.5±2.2天，单用RF治疗的肿瘤为16.6±2.9天，单用脂质体槲皮素治疗的肿瘤为15.5± 2.1天，RF和槲皮素联合治疗的肿瘤为22.0±3.9天。此外，槲皮素/RF/多柔比星联合治疗的生存期最长（48.3±20.4天），其次是RF/多柔比星（29.9±3.8天）。IV脂质体槲皮素联合RF消融可降低肿瘤生长速率并改善动物终点存活率。通过添加额外的抗肿瘤辅助剂脂质体多柔比星，可以看到终点生存率的进一步增加。这表明，用多药物纳米疗法靶向几个消融后过程可以提高总体消融疗效。
To investigate the effect of IV liposomal quercetin (a known down-regulator of heat shock proteins) alone and with liposomal doxorubicin on tumor growth and end-point survival when combined with radiofrequency (RF) tumor ablation in a rat tumor model. Solitary subcutaneous R3230 mammary adenocarcinoma tumors (1.3–1.5 cm) were implanted in 48 female Fischer rats. Initially, 32 tumors (n=8, each group) were randomized into four experimental groups: (a) conventional monopolar RF alone (70°C for 5 min), (b) IV liposomal quercetin alone (1 mg/kg), (c) IV liposomal quercetin followed 24hr later with RF, and (d) no treatment. Next, 16 additional tumors were randomized into two groups (n=8, each) that received a combined RF and liposomal doxorubicin (15 min post-RF, 8 mg/kg) either with or without liposomal quercetin. Kaplan-Meier survival analysis was performed using a tumor diameter of 3.0 cm as the defined survival endpoint. Differences in endpoint survival and tumor doubling time among the groups were highly significant (P<0.001). Endpoint survivals were 12.5±2.2 days for the control group, 16.6±2.9 days for tumors treated with RF alone, 15.5±2.1days for tumors treated with liposomal quercetin alone, and 22.0±3.9 days with combined RF and quercetin. Additionally, combination quercetin/RF/doxorubicin therapy resulted in the longest survival (48.3±20.4 days), followed by RF/doxorubicin (29.9±3.8 days). IV liposomal quercetin in combination with RF ablation reduces tumor growth rates and improves animal endpoint survival. Further increases in endpoint survival can be seen by adding an additional anti-tumor adjuvant agent liposomal doxorubicin. This suggests that targeting several post-ablation processes with multi-drug nanotherapies can increase overall ablation efficacy.
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