REVERSAL OF CHEMORESISTANCE IN MALIGNANT GLIOMAS BY CALCIUM-ANTAGONISTS - CORRELATION WITH THE EXPRESSION OF MULTIDRUG-RESISTANT P-GLYCOPROTEIN

Resistance to multiple drugs is often observed in malignant gliomas. T he authors used a microtiter tetrazolium test to analyze primary in vi tro chemoresistance and chemosensitivity of 15 early cultures of human malignant glioma exposed to 50 mu g/ml yrimidinyl)-methyl-3-(2-chloro ethyl)-3-nitrosourea (ACNU), 50 mu g/ml cisplatin, 1 mu g/ml vincristi ne, or combinations of these chemotherapeutic agents. Primary chemores istance was observed in 87% of tumors for ACNU, in 87% for cisplatin, and in 83% for vincristine. All tumors were examined for expression of multidrug-resistant p-glycoprotein, a transport protein of 170,000 D, by means of immunohistochemical staining with the JSB-1 antibody on p araffinized tumor sections. Eight of 15 specimens (53%) showed positiv e staining for the monoclonal antibody. Primary chemoresistance was ov ercome by addition of the calcium antagonists verapamil or nimodipine to the cultures if the original tumor expressed p-glycoprotein (p < 0. 01 for verapamil, p < 0.05 for nimodipine). In tumors not expressing p -glycoprotein, addition of calcium antagonists to the cell cultures di d not influence primary chemoresistance. It is concluded from these da ta that addition of calcium antagonists to the adjuvant chemotherapy o f malignant gliomas might overcome primary chemoresistance in tumors e xpressing the multidrug-resistant phenotype.