Abstract:
:Limited penetration of anticancer drugs through tumour tissue is an important factor that may limit therapeutic effects against solid tumours. Here we report studies of the penetration of radiolabelled methotrexate through multicellular layers (MCL) of murine EMT-6 and human MCF-7 cells grown on semiporous teflon membranes. The penetration of methotrexate was only about 25% of that through the teflon membrane alone after 6 hr. This was true for all methotrexate concentrations examined from 10 microM to 3 mM. The presence of folic acid at concentrations above 0.1 mM and of acidic conditions decreased the uptake of methotrexate into single cells and enhanced tissue penetration. Hypoxic conditions and the presence of folinic acid (leucovorin) had no effect on penetration or uptake of methotrexate. Our data provide evidence that tissue penetration of methotrexate is through the extracellular space, that its distribution in solid tissue may be limited and that it may be possible to improve its tissue penetration.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Cowan DS,Tannock IFdoi
10.1002/1097-0215(20010101)91:1<120::aid-ijc1021>3keywords:
subject
Has Abstractpub_date
2001-01-01 00:00:00pages
120-5issue
1eissn
0020-7136issn
1097-0215pii
10.1002/1097-0215(20010101)91:1<120::AID-IJC1021>3journal_volume
91pub_type
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