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Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2003-03-0851.
Submitted March 31, 2003
Accepted June 24, 2003
Effect of farnesyl transferase inhibitor R115777 (Zarnestra TM) on the growth of fresh and cloned myeloma cells in vitro
Naoya Ochiai*, Ryo Uchida, Shin-ichi Fuchida, Akira Okano, Masashi Okamoto, Eishi Ashihara, Tohru Inaba, Naohisa Fujita, Hiroaki Matsubara, and Chihiro Shimazaki
Department of Hematology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Department of Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
* Corresponding author; email: naoya{at}koto.kpu-m.ac.jp.
Ras gene mutations occur in 30% to 40% of multiple myeloma (MM) patients, and farnesylation is the first and most important step in the posttranslational modification of Ras proteins. R115777 (Zarnestra TM) is a newly synthesized potent farnesyl transferase inhibitor (FTI) and has recently demonstrated significant antitumor activities in vitro and in vivo. Therefore we examined the effect of R115777 on the growth of fresh and cloned myeloma cells in vitro. R115777 inhibited the growth of fresh and cloned myeloma cells dose-dependently, and effects were not dependent on the status of N-Ras mutation in fresh myeloma cells. Flow cytometric analysis using annexin V and 7AAD showed that R115777 induced apoptosis of two of three myeloma cell lines at a concentration of 1.0x10-8 mol/L. R115777 appears to be a potent inducer of apoptosis and its effects depend on the status of Ras mutation in cloned myeloma cells but not on the status of N-Ras mutation in fresh myeloma cells. This is the first report which demonstrates the relationship between the N-Ras mutation in fresh myeloma cells and the effect of R115777. R115777 might have some benefit in the treatment of myeloma patients.
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