Le-Ruppert, K. and Masters, J. R. and Knuechel, R. and Seegers, S. and Tainsky, M. A. and Hofstaedter, Ferdinand and Buettner, R. (1992) The effect of retinoic acid on chemosensitivity of PA-1 human teratocarcinoma cells and its modulation by an activated N-ras oncogene. International Journal of Cancer 51 (4), pp. 646-651.
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Combination of chemotherapeutic drugs with agents that induce cell differentiation is a possible means of improving cancer chemotherapy. To explore this approach we used 4 cell lines established from the human teratocarcinoma-derived cell line PA-1; 2 retinoic acid (RA)-sensitive lines compared to 2 RA-resistant lines transformed by an activated N-ras oncogene. Equal numbers of colony-forming cells were exposed for 72 hr to 10(-6)M RA and subsequently to a range of concentrations of cisplatinum, etoposide or bleomycin. Enhanced cytotoxicity of cisplatin and etoposide (3- to 5-fold) was observed in the N-ras-transformed cell lines compared to the non-transformed lines. Treatment with RA caused an increase in the cytotoxicity of all 3 drugs to the 2 RA-sensitive cell lines. In contrast, a reduction of cytotoxicity was observed in the 2 N-ras-transformed lines. Our results indicate that sensitivity to cytotoxic agents can be increased by RA in RA-sensitive cells, but the opposite effect is seen in N-ras transformed, RA-resistant cells. Therefore, a general rationale for combination therapy with RA and cytotoxic drugs cannot be inferred.
|Institutions:||Medicine > Lehrstuhl für Pathologie|
|Subjects:||600 Technology > 610 Medical sciences Medicine|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||09 Jun 2010 14:53|
|Last Modified:||09 Jun 2010 14:53|