PRETREATMENT OF HUMAN OSTEOSARCOMA CELLS WITH N-METHYLFORMAMIDE ENHANCES P-GLYCOPROTEIN EXPRESSION AND RESISTANCE TO DOXORUBICIN

N-methylformamide (NMF), a powerful differentiating agent, has been ex tensively used in experimental and preclinical cancer chemotherapy stu dies, alone or in association with conventional anti-cancer drugs. To evaluate the use of this molecule in the treatment of osteosarcoma (OS ), we have analyzed the effects of NMF and doxorubicin (DXR) on DXR-se nsitive and -resistant human OS cell lines. Our study shows that NMF e xerts remarkable effects on cell proliferation and, in Saos-2 and SARG cells, also induces differentiation, as shown by increasing alkaline phosphatase activity. Moreover, NMF increases the cytotoxic activity o f DXR when administered after the drug, in both DXR-sensitive and -res istant cells. However, when this agent is given before DXR, it enhance s P-glycoprotein expression in U-2 OS cell lines. This over-expression is associated with reduced DXR accumulation within cells and with sig nificant enhancement of resistance to DXR. (C) 1994 Wiley-Liss, Inc.