研究概要
这些结果表明,6-MITC 对 EMC 细胞具有显著的抗肿瘤作用,并具有增强 NK 细胞活性的新作用。
中文摘要
目的:山葵是一种具有防腐作用的传统植物调味品。近期研究揭示了山葵的多种功能,例如抗炎作用,但其对子宫内膜癌(EMC)细胞的抗肿瘤作用尚未得到研究。本研究在体外和体内调查了山葵的主要化学成分6-(甲基亚磺酰基)己基异硫氰酸酯(6-MITC)对多种EMC细胞系的抗肿瘤作用。方法:采用WST-1法测定6-MITC对EMC细胞和人脐静脉内皮细胞(HUVEC)存活率的影响;通过对裸鼠口服给予6-MITC,评估其对子宫内膜癌异种移植瘤生长及脾脏自然杀伤(NK)细胞活性的影响。结果:加入6-MITC可剂量依赖性抑制EMC细胞(Ishikawa、HEC265、HEC108、KLE和HEC1B)增殖,但不抑制HUVEC细胞。6-MITC(5 μM)增强了EMC细胞对顺铂的敏感性。除HEC1B细胞外,6-MITC以剂量依赖方式诱导EMC细胞凋亡,并伴随裂解型半胱天冬酶-3表达增加和BCL2表达降低。对携带Ishikawa和HEC1B异种移植瘤的小鼠口服给予6-MITC(2和4 μmol/kg)后,与对照组相比肿瘤体积减小(4 μmol/kg时P<0.05)。切除肿瘤的免疫组织化学染色显示Ki-67表达增加、裂解型半胱天冬酶-3表达降低。此外,6-MITC治疗增强了NK细胞活性,尤其是在肿瘤异种移植前给药时。结论:这些结果表明,6-MITC对子宫内膜癌细胞具有显著抗肿瘤作用,并具有增强NK细胞活性的新作用,提示其具有治疗潜力。
展开英文摘要原文
PURPOSE: Wasabi is a traditional plant seasoning with an anti-septic function. Recent studies revealed several functions of Wasabi, such as anti-inflammation; however, the anti-tumor effect against endometrial carcinoma (EMC) cells has not been examined. In the present study, we investigated the anti-tumor effect of 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), a major chemical compound of Wasabi, against various EMC cell lines in vitro and in vivo.
METHODS: The effect of 6-MITC on cell viability was measured by the WST-1 assay in EMC and HUVEC cells. The impact of 6-MITC oral administration in nude mice was measured to assess the growth of the EMC xenograft and natural killer (NK) cell activity in the spleen.
RESULTS: The addition of 6-MITC suppressed the proliferation of EMC cells (Ishikawa, HEC265, HEC108, KLE, and HEC1B) dose-dependently, but not HUVEC cells. 6-MITC (5 M) enhanced the cisplatin sensitivity of EMC cells. 6-MITC induced apoptosis in a dose-dependent fashion in EMC cells other than HEC1B cells and was associated with increased expression of cleaved-caspase3 and decreased expression of BCL2. Oral administration of 6-MITC (2 and 4 mol/kg) to Ishikawa and HEC1B xenografting mice resulted in a reduced tumor volume compared with the control (P < 0.05, 4 mol/kg). Immunohistochemical staining of resected tumors revealed increased expression of Ki-67 and reduced cleaved-caspase3. Furthermore, 6-MITC treatment enhanced NK cell activity, especially when administered before tumor xenografting.
CONCLUSION: These results indicate that 6-MITC has a marked anti-tumor effect against EMC cells and a novel effect to enhance NK cell activity. These effects suggest the therapeutic potential of 6-MITC.
论文信息
- 作者
- Ono M、Miyamoto T、Fuseya C、Asaka R、Ando H、Tanaka Y、Shinagawa M、Yokokawa Y
- 第一作者单位
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.Japan
- 通讯作者单位
- Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. tmiya@shinshu-u.ac.jp.Japan
- 期刊
- Discover oncology2023 Jan 23