Suppression of lung cancer tumor growth in a nude mouse model by the Ras inhibitor salirasib (farnesylthiosalicylic acid)

• Published in: Molecular cancer therapeutics Vol. 6; no. 6; pp. 1765 - 1773
• Main Authors: Zundelevich, Adi, Elad-Sfadia, Galit, Haklai, Ronit, Kloog, Yoel
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research 01.06.2007
• Subjects: Animals; Antineoplastic Agents - pharmacology; Cell Division - drug effects; Cell Line, Tumor; Farnesol - analogs & derivatives; Farnesol - pharmacology; FTS; gemcitabine; Humans; lung cancer; Lung Neoplasms - pathology; Mice; Mice, Nude; Ras; ras Proteins - antagonists & inhibitors; Salicylates - pharmacology; salirasib
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.MCT-06-0706

Aberrant Ras pathway functions contribute to the malignant phenotype of lung cancers. Inhibitors of Ras might therefore be considered as potential drugs for lung cancer therapy. Here, we show that the Ras inhibitor farnesylthiosalicylic acid (salirasib) inhibits proliferation of human lung cancer cells harboring a mutated K-ras gene (A549, H23, or HTB54) or overexpressing a growth factor receptor (H1299 or HTB58) and enhances the cytotoxic effect of the chemotherapeutic drug gemcitabine. Salirasib inhibited active K-Ras in A549 cells, reversed their transformed morphology, and inhibited their anchorage-independent growth in vitro . Tumor growth in A549 and HTB58 cell nude mouse models was inhibited by i.p. administration of salirasib. P.o. formulated salirasib also inhibited A549 cell tumor growth. Our results suggest that p.o. salirasib may be considered as a potential treatment for lung cancer therapy. [Mol Cancer Ther 2007;6(6):1765–1773]