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Pre‐Treatment of human osteosarcoma cells with N‐methylformamide enhances P‐glycoprotein expression and resistance to doxorubicin
Author(s) -
Scotlandi Katia,
Serra Massimo,
Manara Maria Cristina,
Lollini PierLuigi,
Maurici Daniela,
Bufalo Donatella Del,
Baldini Nicola
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580116
Subject(s) - osteosarcoma , doxorubicin , cancer research , p glycoprotein , cytotoxic t cell , cancer cell , cell , cell growth , chemistry , cell culture , drug resistance , chemotherapy , alkaline phosphatase , cancer , biology , pharmacology , in vitro , medicine , multiple drug resistance , biochemistry , enzyme , genetics
N‐methylformamide (NMF), 3 powerful differentiating agent, has been extensively used in experimental and preclinical cancer chemotherapy studies, alone or in association with conventional anti‐cancer drugs. To evaluate the use of this molecule in the treatment of osteosarcoms (OS), we have analyzed the effects of NMF and doxorubicin (DXR) or DXR‐sensitive and ‐resistant human OS cell lines. Our study shows that NMF exerts 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 of DXR when administered after the drug, In both DXR‐sensitive and ‐resistant cells. However, when this agent is given before DXR, it enhances P‐glycoprotein expression in U‐2 OS cell lines. This over‐expression is associated with reduced DXR accumulation within cells and with significant enhancement of resistance to DXR. © 1994 Wiley‐Liss, Inc.