2002 Fiscal Year Final Research Report Summary

INVESTIGATION OF HIF-1α TARGET MOLECULE THERAPY OF SOLID TUMORUNDER STRESS CONDITIONS

Research Project

Project/Area Number	13470433
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Surgical dentistry
Research Institution	OKAYAMA UNIVERSITY
Principal Investigator	MATSUMURA Tomohiro OKAYAMA UNIVERSITY GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 教授 (00028747)
Co-Investigator(Kenkyū-buntansha)	MESE Hiroshi OKAYAMA UNIVERSITY, DENTAL SCHOOL, LECTURER, 歯学部附属病院, 講師 (40325098) SASAKI Akira OKAYAMA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE AND DENTISTRY, ASSOCIATE PROFESSOR, 大学院・医歯学総合研究科, 助教授 (00170663)
Project Period (FY)	2001 – 2002
Keywords	oral squamous cell carcinoma / stress conditions solid tumors / hypoxia / molecular target therapy / HIF-1 α / Cisplatin(CDDP)
Research Abstract	Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates genes involved in adaptation to hypoxia. Tissue hypoxia is critical in tumor formation, where it has been associated with malignant progression and resistance to radiotherapy and chemotherapy. We analyzed oral squamous cell carcinoma cell lines (HSC2, HSC3, HSC4, KB, T3M1, KOSC3, SAS and Hol-ul). Under hypoxia condition (10% O_2) we detected HF-1 αprotein by western blotting. Expression of this protein was time dependent manner. In these cell lines, HTF-1 αinduced vascular endothelial growth factor (VEGF) protein, but not p-53 protein. The anti-cancer drug sensitivity was determined by dye exclusion assay. The Cisplatin sensitivity was significantly increased under hypoxia condition (1%O_2). However, other anti-cancer drug (ADM, BLM, T-FU and TXL) sensitivity was no change under hypoxia condition. Next, we examined differences of cell cycle between hypoxia and normoxia condition treated with Cisplatin. Under hypoxia condition treated with Cisplatin, these cell lines were not accumulated the cell cyde into G2-M phase. In summary, our studies indicated that oral squamous cell carcinoma cell lines were hypersensitive to Cisplatin under hypoxia condition. We believed that such an examination would lead to discover of new strategy for clinical effectiveness of Cisplatin under hypoxia condition.