Increase of alkaline phosphatase in multidrug-resistant tumor cells and their cross-resistance to 6-thioguanine.
The expression of alkaline phosphatase (AP) was analyzed in multidrug-resistant (MDR) tumor cells (sarcoma 180, lung carcinoma, and renal cell carcinoma cell lines) by means of immunocytochemistry. MDR cell cultures showed an overexpression of AP and a cross-resistance to 6-thioguanine (6-TG, CAS 154-42-7). Significant correlations between AP expression and doxorubicin or vincristine resistance and P-glycoprotein (P-170) expression were found in these cell cultures. A specific AP inhibitor, levamisole, reversed resistance to 6-TG, but not to doxorubicin. This indicates that 6-TG resistance is certainly associated to P-170 but a causal function of AP for the development of MDR does not exist.
Efferth
T
T
German Cancer Research Center, Heidelberg.
Volm
M
M
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000201:enzymology*; D002455:Cell Division / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D006801:Humans; D007150:Immunohistochemistry; D007978:Levamisole / Q000494:pharmacology; D051379:Mice; D011863:Radioimmunoassay; D012510:Sarcoma 180 / Q000188:drug therapy / Q000201:enzymology*; D013866:Thioguanine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D007978:Levamisole; D014750:Vincristine; D004317:Doxorubicin; D000469:Alkaline Phosphatase; D013866:Thioguanine