Tumor-selective blood flow decrease induced by an angiotensin converting enzyme inhibitor, temocapril hydrochloride.
To enhance chemotherapeutic efficacy against cancer, it is important to deliver anticancer drugs preferentially to cancer cells and to retain the drugs there for a prolonged time. The in vivo prolongation of the exposure time of anticancer drugs in tumors can be accomplished by decreasing tumor tissue blood flow (tBF) after anticancer drug administration. The present study demonstrated that temocapril hydrochloride, an angiotensin converting enzyme inhibitor, decreases tumor tBF markedly in LY80 tumor, a subline of Yoshida sarcoma in the rat, without affecting the blood flow in liver, kidney, bone marrow, and brain. In tumor areas with flow of above 20 ml/min/100 g, the tBF decreased by approximately 50% due to temocapril. In tumor areas with tBF of about 20 ml/min/100 g, it became less than 3 ml/min/100 g with temocapril and did not recover during the 2 h experiment. These findings were obtained not only in large tumors, but also in microfoci growing within a transparent chamber. Furthermore, even when temocapril was administered under the condition of increased tumor tBF by administering angiotensin II, tumor tBF decreased immediately. Using this technique, it should be possible to trap anticancer drugs selectively in tumor tissue for an extended period of time.
Hori
K
K
Department of Vascular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai. k-hori@idac.tohoku.ac.jp
Saito
S
S
Takahashi
H
H
Sato
H
H
Maeda
H
H
Sato
Y
Y
D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D008297:Male; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D012513:Sarcoma, Experimental / Q000098:blood supply* / Q000188:drug therapy; D013841:Thiazepines / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D013841:Thiazepines; D000804:Angiotensin II; C055603:temocapril hydrochloride