ICEECE2012 Poster Presentations Endocrine tumours and neoplasia (112 abstracts)
Enhanced antitumor efficacy of fructose conjugated-gefitinib on lung cancer cell lines in vitro and in vivo
H. Hui 1, , S. Zhang 3 , W. Ding 1, , J. Li 2 , X. Zhao 1, , M. Zuo 3 , X. Wang 3 , W. Gu 4 , S. Pandol 2, & V. Go 2,
David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Cancer cells have shown an overexpressed fructose transporter GLUT5 and preferential utilization of fructose as compared to glucose, implicating that a fructose-based analogue would be a useful target for diagnosis and treatment of cancer. We have successfully synthesized the fructose conjugated-gefitinib compounds {N-[4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-7-methoxy-quinazolin-6-yl]-4- [N-methyl-N-(1-deoxy-1-fructosyl)]aminobutanamide}, and examined its antitumor efficacy on cancer cell lines in vitro and in vivo. Conjugation of fuctose with gefitinib, a sparingly water-soluble drug, dramatically improved its aqueous solubility. Dose-and time-dependently anti-proliferation and apoptosis effect of fructose-gefitinib compound 1 have been observed with MTT assay and FACS in both human colon adenocarcinoma cell line SW480 and human lung adenocarcinoma epithelial cell line A549, the median IC50 values of compound 1 for SW480 and A549 cell lines at exposure durations of 72 h were 2.96 μM and 10.69μM, considerably lower than 8.26 μM and 21.4 μM of gefitinib on SW480 and A549 cell lines, respectively. Furthermore, its attenuated efficacy have been observed in cells trasfected with Glut5 SiRNA. In addition, the enhanced antitumor effects of the compound I was confirmed in A549 tumor xenograft models. Our data demonstrate, for the first time, that conjugation of fuctose and gefitinib imporved the solobility and ehnhanced antitumor effect of gefitinib on lung cancer in vitro and in vivo, at least, via increased fructose-medicated gefitinib uptake, and suggest that metabolic characterization of cancer could be a potential target for diagnosis and treatment.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more