MODULATION OF MULTIDRUG-RESISTANCE BY CEPHARANTHINE IN FRESH HUMAN GASTROINTESTINAL TUMOR-CELLS

Resistance to doxorubicin (DOX) is mainly due to the effect of P-glyco protein encoded by the multidrug resistance (MDR) gene. Cepharanthine (CEP) has been shown to circumvent multidrug resistance in P-glycoprot ein-expressing cell lines. In the present study, we investigated the a ugmentation of DOX sensitivity by CEP using an MTT assay, and assessed the correlation between DOX sensitivity and P-glycoprotein expression by flow cytometry, in highly purified fresh human tumor cells obtaine d from 73 cancer patients. DOX sensitivity was decreased in proportion to P-glycoprotein expression. The cytotoxicity of DOX was increased b y CEP in tumor cells possessing low DOX P-glycoprotein sensitivity. Mo reover, there was a significant correlation between the effect of Doxo rubicin CEP on cytotoxicity and P-glycoprotein expression. Thus, CEP m ight be able Cepharanthine to circumvent DOX resistance in cancer pati ents.