Angiotensin II-induced hypertension enhanced therapeutic efficacy of liposomal doxorubicin in tumor-bearing mice.

In this study, we investigated whether the therapeutic efficacy of liposomal doxorubicin (DXR-SL) could be enhanced by angiotensin II (AT)-induced hypertension. AT-induced hypertension increased the volume of tumor blood flow in mice bearing a poorly vascularized Lewis lung carcinoma (LLC) tumor, but only slightly in mice bearing a well-vascularized colon carcinoma Colon 26 (C26) tumor. In therapeutic efficacy, AT-induced hypertension enhanced the antitumor activity of DXR-SL in mice bearing LLC and C26 tumors. Localization of DXR-SL after injection by AT-induced hypertension was observed outside tumor blood vessels in LLC and C26 tumors, but within them under the normotension. From these findings, AT-induced hypertension had potential to improve the delivery of DXR-SL to both well- and poorly vascularized solid tumors.