目的:山葵是一种具有防腐功能的传统植物调味料。最近的研究揭示了山葵的几个功能,如抗炎;然而,对子宫内膜癌(EMC)细胞的抗肿瘤作用尚未研究。在本研究中,我们研究了6-(甲基亚磺酰基)异硫氰酸己酯(6-MITC)的抗肿瘤作用,山葵的主要化合物,在体外和体内对抗各种EMC细胞系。
方法:通过EMC和HUVEC细胞中的WST-1测定来测量6-MITC对细胞活力的影响。测量6-MITC口服施用在裸小鼠中的影响以评估EMC异种移植物的生长和脾脏中的自然杀伤(NK)细胞活性。
结果:添加6-MITC抑制了EMC细胞的增殖(Ishikawa,HEC265HEC108KLE,和HEC1B)剂量依赖性,但不是HUVEC细胞。6-MITC(5µM)增强了EMC细胞的顺铂敏感性。6-MITC在除HEC1B细胞以外的EMC细胞中以剂量依赖性方式诱导细胞凋亡,并且与裂解的caspase3的表达增加和BCL2的表达减少有关。与对照组相比,对Ishikawa和HEC1B异种移植小鼠口服6-MITC(2和4µmol/kg)导致肿瘤体积减小(P<0.05,4µmol/kg)。切除肿瘤的免疫组织化学染色显示Ki-67的表达增加,caspase3的切割减少。此外,6-MITC处理增强NK细胞活性,特别是在肿瘤异种移植前给药。
结论:这些结果表明,6-MITC对EMC细胞具有明显的抗肿瘤作用,并具有增强NK细胞活性的新作用。这些效应表明6-MITC的治疗潜力。
OBJECTIVE: 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 µM) 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 µmol/kg) to Ishikawa and HEC1B xenografting mice resulted in a reduced tumor volume compared with the control (P < 0.05, 4 µmol/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.
CONCLUSIONS: 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.