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Abstract
Background. The high interstitial fluid pressure (IFP) in solid tumors restricts the access to nutrients, oxygen and drugs. Material and methods. We investigated the ability of the peptide AF-16, involved in water and ion transfer through cell membranes, to lower the IFP in two different solid rat mammary tumors, one chemically induced, slowly growing, and the other transplantable, and rapidly progressing having high cellularity. AF-16 was administered either in the tumor capsule, intranasally or intravenously. The IFP was measured by a miniature fiber optic device. Results. AF-16 significantly lowered the IFP in both the slowly and the rapidly progressing tumors, whether administrated locally or systemically. The AF-16 induced IFP reduction was maximal after 90 min, lasted at least 3 h, and returned to pretreatment levels in less than 24 h. Topical AF-16 transiently reduced the IFP in the DMBA tumors from 17.7 ± 4.2 mmHg to 8.6 ± 2.1 mmHg. Conclusion. We conclude that AF-16 transiently and reversibly lowered the high IFP in solid tumors during a few hours, which might translate into improved therapeutic efficacy.
Acknowledgments
We thank Dr. Svante Höjer, Samba Sensors AB, for advices, support and help; Professor Ingvar Bosaeus for expert statistical advice; Ingela Jonsson and Margareta Rosenkvist for invaluable technical assistance. This work was in parts presented 2010 at an AACR conference on Tumor Immunology: basic and clinical advances, Miami, Florida, USA (# B9). Grant support from the Swedish federal government under the LUA/ALF agreement (grant # 71570), Sahlgrenska University Hospital (grant # 83030), the Ministry of High Education UAE, Magnus Bergvall Foundation, W. and M. Lundgren Foundation, Frimurare- Barnhus direktionen, Göteborg Medical Society, AB Nectin, and Lantmännen AS-Faktor AB.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.