Analysis of role of CDKN3 in taxan resistant human head and neck cancer

Research Project

Project/Area Number	15K20195
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Otorhinolaryngology
Research Institution	University of Fukui
Principal Investigator	Ito Yumi 福井大学, 学術研究院医学系部門(附属病院部), 特命助教 (00646458)
Project Period (FY)	2015-04-01 – 2017-03-31
Project Status	Completed (Fiscal Year 2016)
Budget Amount *help	¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000) Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000) Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	CDKN3 / タキサン耐性 / 頭頸部癌 / 頭頚部扁平上皮癌 / タキソール耐性
Outline of Final Research Achievements	We established paclitaxel-resistant cancer cell line T3M-1 TX, from T3M-1 human oropharyngeal cancer cell line. T3M-1TX cells have docetaxel resistance in addition to paclitaxel. T3M-1TX cells show that paclitaxel treatment induces G1/S arrest and G2/M transition of the cell cycle. In the result of PCR array, we focused on Cyclin dependent kinase inhibitor 3 (CDKN3), a regulator of G1/S arrest and G2/M transition. The specific siRNA for CDKN3 reduced the expression of CDKN3, resulting in enhanced apoptosis after paclitaxel and docetaxel treatment. The MTT assays and clonogenic cell survival assays proved that inhibition of CDKN3 reduced cell viability after paclitaxel and docetaxel treatment. CDKN3 is a novel molecular target to overcome taxane-resistance of head and neck cancers.