Document Detail

Downregulation of midkine induces cisplatin resistance in human oral squamous cell carcinoma.
MedLine Citation:
PMID:  22344722     Owner:  NLM     Status:  Publisher    
The presence of drug-resistant cancer cells has been associated with poor clinical outcomes. Cisplatin is one of the most effective chemotherapeutic agents commonly used for several malignancies including oral squamous cell carcinoma (OSCC). Although cisplatin resistance is a major obstacle in cancer treatment, mechanisms by which it develops are not well understood. Midkine (MK), a heparin-binding growth factor, has various cancer-related functions. In this study, we investigated whether MK is involved in cisplatin resistance in OSCC. We demonstrated that the Sa-3R cell line, which is OSCC cisplatin-resistant, exhibited lower MK expression with slow growth compared with its parent, Sa-3 cells. In Sa-3 cells, downregulation of MK expression significantly reduced cisplatin sensitivity, cell growth, and the expression of cyclin D1 and cyclin E1. MK knockdown suppressed cellular cisplatin accumulation via induction of ATP-binding cassette efflux transporters. These data suggest that MK may play important roles in cisplatin resistance in OSCC by modulating both cell growth and intracellular cisplatin accumulation.
Tomoko Ota; Hirofumi Jono; Kazutoshi Ota; Satoru Shinriki; Mitsuharu Ueda; Takanao Sueyoshi; Ken Nakatani; Yukihiro Hiraishi; Takeshi Wada; Shigeyuki Fujita; Konen Obayashi; Masanori Shinohara; Yukio Ando
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-13
Journal Detail:
Title:  Oncology reports     Volume:  -     ISSN:  1791-2431     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
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