A novel therapeutic method for uterine cervical cancer by Arsenic trioxide via inducing Carbonyl reductase 1

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18222
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Yamaguchi University
• Principal Investigator: Kajimura Takuya 山口大学, 医学部附属病院, 助教 (20780779)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 三酸化二砒素 / Carbonyl reducatase 1 / 子宮頸癌

Outline of Final Research Achievements

Arsenic trioxide (ATO) is known as the inducer for Carbonyl reductase 1 (CBR1), which reduces the malignant behavior of uterine cervical cancer. However, it is still unclear if ATO can increase the CBR1 in uterine cervical cancer, and can have the therapeutic effect in uterine cervical cancer. We assessed how ATO affects in uterine cervical cancer via CBR1. ATO induced CBR1 expression and suppresses the abilities of proliferation and invasion in uterine cervical cancer cell lines (SiHa and SKGII). We established the cervical cancer model by using nude mice, which were transplanted cervical cancer cell-lines under the skin. After 5 mg/kg ATO was injected for 8 weeks, the tumorigenesis was significantly reduced. Also, the CBR1 expression level in the tumors was significantly lower than those in the control.
These results suggested that ATO can be a novel therapeutic method of uterine cervical cancer.

Free Research Field

産婦人科

Academic Significance and Societal Importance of the Research Achievements

子宮頸癌治療として手術による病巣除去と白金系の抗癌剤投与が標準療法として確立され、またヒトパピローマウィルスに対する予防ワクチンの開発により子宮頸癌の発症率低下が期待されたが、未だに同疾患は若年女性の死因の上位を占めており再発症例の治療は困難であり、そうした症例に対する新たな治療法の開発が急務である。三酸化二砒素(ATO)は、白血病の治療薬としてすでに臨床現場では広く使われておりその安全性などの情報も知られている。すでに臨床上の使用条件の明らかな薬剤であるATOが使用できれば即座に臨床応用が可能であり、既存の抗癌剤に抵抗性の症例に対する新たな治療方法として非常に有望な手段となる可能性がある。