Lowering of tumoral interstitial fluid pressure by prostaglandin E(1) is paralleled by an increased uptake of (51)Cr-EDTA.
High intra-tumoral fluid pressure (TP(IF)) may impair uptake of anticancer drugs into tumors, contributing to poor efficiency in treatment of carcinomas. Here, we demonstrate that lowering of TP(IF) parallels increased transport of (51)Cr-EDTA (m.w. 341) into tumor interstitium. Introduction of 15 microg prostaglandin E(1) (PGE(1)) -methyl ester into the s.c. tissue surrounding transplanted rat colonic (PROb) carcinomas or chemically-induced rat mammary carcinomas, lowered TP(IF) by 30%. Transcapillary transport into the interstitium of PROb tumors quantified by microdialysis increased by 39.6% after PGE(1) treatment 40 min prior to administration of (51)Cr-EDTA (n=6; p<0.05) compared to vehicle (n=10). In mammary tumors, PGE(1) increased transport into the tumors by 86.9% over controls (n=16; p<0.05). Both tumors had well developed stroma containing collagen and hyaluronan. Our data demonstrate that adjuvant treatment with PGE(1) lowers TP(IF), and enhances transport into the tumors. This principle may be of value as adjuvant therapy in treatment of solid malignancies with currently used anticancer drugs.
Rubin
K
K
Department of Medical Biochemistry and Microbiology, University of Uppsala, Uppsala, Sweden. rubin@medkem.uu.se
Sjöquist
M
M
Gustafsson
A M
AM
Isaksson
B
B
Salvessen
G
G
Reed
R K
RK
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D001794:Blood Pressure / Q000187:drug effects; D002021:Buffers; D004492:Edetic Acid / Q000493:pharmacokinetics*; D011464:Epoprostenol / Q000494:pharmacology; D005110:Extracellular Space; D005260:Female; D017551:Microdialysis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley
D002021:Buffers; D004492:Edetic Acid; D011464:Epoprostenol; D000527:Alprostadil