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

BackgroundTo 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.MethodsSolitary 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 24 hr 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.ResultsDifferences 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 ± 2.1 days 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).ConclusionsIV 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.

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.Figure optionsDownload high-quality image (302 K)Download as PowerPoint slide