Increased sensitivity to cisplatin in non-small cell lung cancer cell lines after FHIT gene transfer

Neoplasia : an International Journal for Oncology Research
F AndrianiL Roz

Abstract

To evaluate the relevance of fragile histidine triad (FHIT) status in relation to drug treatment, we analyzed the sensitivity of the Fhit-negative non-small cell lung cancer (NSCLC) cell line NCI-H460 to different drugs, after treatment with an adenoviral vector expressing the FHIT transgene. Expression of Fhit resulted in reduced sensitivity to etoposide, doxorubicin, and topotecan. This feature was associated with Fhit-induced downregulation of DNA topoisomerases I and II. In contrast, expression of Fhit did not modulate sensitivity to Taxol, but produced a slight increase in sensitivity to cisplatin, as shown by colony-forming assays. Analysis of apoptosis revealed that, after cisplatin exposure, the number of apoptotic cells was two-fold higher in Fhit-expressing H460 cells. Moreover, it appeared that wildtype p53 was required for sensitization to cisplatin because the effect was marginal in A549 and Calu-1 cells, where the p53 pathway is altered and simultaneous restoration of p53 and Fhit in Calu-1 cells increased cisplatin sensitivity. Fhit could also partially restore sensitivity to cisplatin in Bcl-2- and Bcl-x(L)-overexpressing H460 cells that are normally resistant to this drug. Our results support the possible relev...Continue Reading

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Citations

Apr 17, 2014·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Jacqueline Gamboa VarelaJose E Nuñez
Jun 7, 2011·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Kwang Woon KimBo Lu
Mar 20, 2012·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Francesca AndrianiLuca Roz
Jun 3, 2009·Cancer Science·Hiroshi OkumuraKay Huebner
Sep 16, 2015·Chemical Research in Toxicology·Lucas Lourenço MarosticaCláudia Maria Oliveira Simões
Dec 9, 2014·Cell Cycle·Jennifer A Boylston, Charles Brenner
Sep 25, 2012·Cellular Signalling·Fereshteh Mir MohammadrezaeiMohammad Hossein Ghahremani
Sep 15, 2017·International Journal of Cancer. Journal International Du Cancer·Jennifer L BryantAnne White
Sep 13, 2008·American Journal of Respiratory and Critical Care Medicine·Gabriella SozziUgo Pastorino
Apr 3, 2020·International Journal of Oncology·Alice ZamagniChiara Molinari

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