Anti-tumor efficacy of interventional chemotherapy with liposomal doxorubicin for hepatic metastasis of pancreatic cancer in nude mouse model

Abstract

To investigate the anti-tumor effect of interventional chemotherapy with liposome doxorubicin for hepatic metastasis of pancreatic tumor in nude mice. After the establishment of hepatic metastatic model of pancreatic tumor, the nude mice received various formulations via a spleen injection to imitate the interventional chemotherapy. In each of two following experiments, 42 nude mice were randomly divided into 6 groups. They received liposomal doxorubicin (including high, intermittent and low-dose), free doxorubicin, gemcitabine plus cisplatin and control respectively. In the first experiment, the doses were 6, 3, 1.5, 3, 3 mg/kg and 100 µl 10% glucose for each group respectively. And in the second experiment, 9, 6, 3, 6, 6 mg/kg, and 100 µl 10% glucose respectively. The efficacies of interventional injection of liposomal doxorubicin with different doses were examined in terms of tumor growth retardation for the hepatic metastatic foci of pancreatic tumor. In the first experiment, the difference of median hepatic tumor volume was significant among the three groups of mice receiving liposomal doxorubicin with incremental doses in a dose-dependent manner [high dose: (3 ± 1) mm(3), middle dose: (55 ± 18) mm(3), low dose: (90 ± 23) mm(3), P < 0.05]. The liposomal doxorubicin led to a substantial delay of tumor growth as compared to the free drug or gemcitabine plus cisplatin at the same dose (both P < 0.05). In addition, all animals were well-tolerated with no obvious acute toxicity. In the second experiment, significant difference was obtained for the mice injected with different doses of liposomal doxorubicin [(11 ± 4) mm(3), (13 ± 4) mm(3), (50 ± 18) mm(3), P < 0.05]. It was correlated with tumor growth delay. The mice administered with either 9 mg/kg or 6 mg/kg were more efficacious to retard tumor growth than those given 3 mg/kg (P < 0.05). Despite its enhanced effectiveness as compared to mice in gemcitabine plus cisplatin group (P < 0.05), the liposomal doxorubicin at a dose of 6 mg/kg resulted in a marginally delayed tumor growth compared to those of free doxorubicin at the same dose (P > 0.05). No evident acute toxic response was observed for each group of mice receiving liposomal doxorubicin. In contrast, approximately half of the animals receiving either free doxorubicin or gemcitabine plus cisplatin died of toxic responses. Liposomal doxorubicin may be a potential interventional chemotherapeutic agent for hepatic metastasis of pancreatic tumor because of improved anti-tumor efficacy and reduced toxicity in comparison to free doxorubicin and gemcitabine plus cisplatin.