Enhanced expression of nuclear factor I/B in oxaliplatin‐resistant human cancer cell lines

• Published in: Cancer science Vol. 102; no. 2; pp. 382 - 386
• Main Authors: Kashiwagi, Eiji, Izumi, Hiroto, Yasuniwa, Yoshihiro, Baba, Ryoko, Doi, Yoshiaki, Kidani, Akihiko, Arao, Tokuzo, Nishio, Kazuto, Naito, Seiji, Kohno, Kimitoshi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-02-2011; Blackwell
• Subjects: Antineoplastic Agents - pharmacology; Biological and medical sciences; Biomarkers, Tumor - genetics; Blotting, Western; Cell Line, Tumor; Drug Resistance, Neoplasm - genetics; Gene Expression Profiling; Humans; Medical sciences; Neoplasms - genetics; Neoplasms - metabolism; NFI Transcription Factors - biosynthesis; NFI Transcription Factors - genetics; Oligonucleotide Array Sequence Analysis; Organoplatinum Compounds - pharmacology; Tumors; Antineoplastic agent; Human; Resistance; Alkylating agent; Cancerology; Oxaliplatin; Established cell line; Complement factor B; Transcription factor; Tumor cell; Platinum II Complexes
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/j.1349-7006.2010.01784.x

Oxaliplatin is a third‐generation platinum drug that has favorable activity in cisplatin‐resistant cells. However, the molecular mechanisms underlying oxaliplatin resistance are not well understood. To investigate the molecular mechanisms involved, resistant cell lines were independently derived from colon cancer (DLD1) and bladder cancer (T24) cells. Oxaliplatin‐resistant DLD1 OX1 and DLD1 OX2 cell lines were approximately 16.3‐fold and 17.8‐fold more resistant to oxaliplatin than the parent cell lines, respectively, and had 1.7‐ and 2.2‐fold higher cross‐resistance to cisplatin, respectively. Oxaliplatin‐resistant T24 OX2 and T24 OX3 cell lines were approximately 5.0‐fold more resistant to oxaliplatin than the parent cell line and had 1.9‐fold higher cross‐resistance to cisplatin. One hundred and fifty‐eight genes commonly upregulated in both DLD1 OX1 and DLD1 OX2 were identified by microarray analysis. These genes were mainly involved in the function of transcriptional regulators (14.6%), metabolic molecules (14.6%), and transporters (9.5%). Of these, nuclear factor I/B (NFIB) was upregulated in all oxaliplatin‐resistant cells. Downregulation of NFIB rendered cells sensitive to oxaliplatin, but not to cisplatin. Forced expression of NFIB induced resistance to oxaliplatin, but not to cisplatin. Taken together, these results suggest that NFIB is a novel and specific biomarker for oxaliplatin resistance in human cancers. (Cancer Sci 2011; 102: 382–386)