J Control Release. 2011 Dec 30. [Epub ahead of print]
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.
Laboratory for Minimally Invasive Tumor Therapies, Department of Radiology, Beth Israel Deaconess Medical Center/Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, United States; Key laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Ultrasound, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing 100142, China.
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 (1.3-1.5cm) were implanted in 48 female Fischer rats.
Initially, 32 tumors (n=8, each group) were randomized into four experimental groups:
- conventional monopolar RF alone (70°C for 5min),
- IV liposomal quercetin alone (1mg/kg),
- IV liposomal quercetin followed 24hr later with RF, and
- no treatment.
Next, 16 additional tumors were randomized into two groups (n=8, each) that received a combined RF and liposomal doxorubicin (15min post-RF, 8mg/kg) either with or without liposomal quercetin.
Kaplan-Meier survival analysis was performed using a tumor diameter of 3.0cm 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±2.2days for the control group, 16.6±2.9days for tumors treated with RF alone, 15.5±2.1days for tumors treated with liposomal quercetin alone, and 22.0±3.9days with combined RF and quercetin. Additionally, combination quercetin/RF/doxorubicin therapy resulted in the longest survival (48.3±20.4days), followed by RF/doxorubicin (29.9±3.8days).
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.
Copyright © 2011 Elsevier B.V. All rights reserved.