TAMOXIFEN CIRCUMVENTS THE MULTIDRUG-RESISTANCE IN FRESH HUMAN GASTROINTESTINAL CANCER-CELLS

The resistance to doxorubicin (DOX) is mainly due to the effect of P-g lycoprotein encoded by the multidrug resistance-1 (mdr1) gene. Tamoxif en (TAM) has been shown to circumvent multidrug resistance in P-glycop rotein-expressing cell lines. In the present study, we clarified the a ugmentation of DOX sensitivity by TAM using MTT assay in highly purifi ed fresh human tumor cells obtained from 85 cancer patients. Moreover, the correlation between DOX sensitivity and P-glycoprotein expression was assessed by how cytometry. DOX sensitivity was decreased in propo rtion to P-glycoprotein expression. The cytotoxicity of DOX was increa sed by TAM in tumor cells possessing low DOX sensitivity. Moreover, th ere was a significant correlation between the effect of TAM on cytotox icity and P-glycoprotein expression. The concentration of DOX in tumor cells was increased in combined exposure of TAM with DOX, compared wi th the exposure of DOX alone. Thus, TAM might be able to circumvent DO X-resistance for treatment in cancer patients. (C) 1996 Academic Press , Inc.