Molecular basis analysis of anticancer effect by combined arsenic trioxide-cisplatin treatment and development of efficient chemotherapy

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K17115
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Aichi Medical University
• Principal Investigator: Ono Takayuki 愛知医科大学, 医学部, 講師 (20434623)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: Arsenic trioxide / chemotherapy / squamous cell carcinoma / Apoptosis / Reactive oxygen species / Cisplatin / 細胞接着関連遺伝子

Outline of Final Research Achievements

We assessed the efficacy of a combinatorial arsenic trioxide (ATO) and cisplatin (CDDP) treatment in human OSCC cells.The combinational effect of ATO/CDDP on the growth and apoptosis of OSCC cell lines was evaluated using MTT assay. ChouーTalalay analyses were preformed to evaluate the combinational effects of ATO/CDDP on the dosereduction index (DRI). Combination index (CI) analyses revealed that a synergistic interaction of ATO and CDDP elicits a wide range of effects. As a result, a synergistic effect was recognized, and it was shown that drug reduction was possible.
To clarify the mechanism underlying the ATO/CDDP anticancer effect, we also performed microarray analysis and GSEA. As a result, it was strongly suggested that ATO / CDDP may induced ROS production, reduced the activity of cancer-related genes and cell adhesion-related genes at the transcriptional level, and induced apoptosis of OSCC cells.

Free Research Field

口腔外科学

Academic Significance and Societal Importance of the Research Achievements

近年、口腔癌に対しては三種併用療法が主流となっている。しかしながら、再発・転移症例に対する十分な治療法は未だ確立されていない。このような現状を打破するためには、新たな治療法の開発、または既存の治療法の更なる効率化を図ることが必要である。そこで、口腔癌に対する新たな治療戦略を提供するために、近年注目されている抗がん剤である三酸化ヒ素(以下ATO)に着目した。
本研究において、ATOとCDDPの併用療法による抗腫瘍効果の増強作用、薬剤投与量の低減作用および細胞死の作用機序に寄与すると示唆される遺伝子発現を同定できたことは、現在の治療法の更なる効率化や新規治療法の開発へと道を開く一助となる。