Liu Xiaohong, Sun Kai, Song Ailin, Zhang Xiaoyun, Zhang Xu, He Xiaodong
Department of General Surgery, second affiliated hospital of Lanzhou University, Lanzhou, Gansu, 730000, China.
The Second Department of Thoracic Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.
World J Surg Oncol. 2014 Dec 19;12:389. doi: 10.1186/1477-7819-12-389.
This study was aimed to investigate whether ATP-sensitive potassium channel (KATP) is involved in curcumin's anti-proliferative effects against gastric cancer.
In an in vitro study, gastric cancer cell line SGC-7901 was treated with curcumin at serial concentrations and co-administrated with the KATP opener, diazoxide. The effect of curcumin and diazoxide on proliferation were assessed by MTT assay. Mitochondrial membrane potential (MMP) was studied by flow cytometry detection of rhodamine 123 staining. Apoptosis was evaluated by flow cytometry detection of Annexin V propidium iodide double staining. In an in vivo study, SGC-7901 cells were planted into nude mice as xenografts. Animals were treated with curcumin co-administered with diazoxide. Tumor volume and tumor weight were observed.
Curcumin incubation significantly induced loss of MMP in SGC-7901 cells in a dose- dependent manner (P < 0.05); the cell apoptotic rate also dramatically increased after curcumin incubation in a dose-dependent manner (P < 0.05). After co-administration with diazoxide, however, we found that both the MMP-loss-inducing and the apoptosis-inducing effects of curcumin in SGC-7901 cells were significantly impaired (all P < 0.05). As a result, the proliferation of SGC-7901 cells was maintained by diazoxide treatment.
Impaired mitoKATP opening causes MMP loss, and is involved in curcumin-induced apoptosis in gastric cancer.
本研究旨在探讨三磷酸腺苷敏感性钾通道（KATP）是否参与姜黄素对胃癌的抗增殖作用。
在体外研究中，用不同浓度的姜黄素处理胃癌细胞系SGC-7901，并与KATP开放剂二氮嗪共同给药。通过MTT法评估姜黄素和二氮嗪对细胞增殖的影响。通过流式细胞术检测罗丹明123染色来研究线粒体膜电位（MMP）。通过流式细胞术检测膜联蛋白V碘化丙啶双染来评估细胞凋亡。在体内研究中，将SGC-7901细胞接种到裸鼠体内作为异种移植物。动物接受姜黄素与二氮嗪联合给药治疗。观察肿瘤体积和肿瘤重量。
姜黄素孵育能以剂量依赖性方式显著诱导SGC-7901细胞的MMP丧失（P < 0.05）；姜黄素孵育后细胞凋亡率也以剂量依赖性方式显著增加（P < 0.05）。然而，与二氮嗪共同给药后，我们发现姜黄素对SGC-7901细胞的MMP丧失诱导作用和凋亡诱导作用均显著受损（所有P < 0.05）。结果，二氮嗪处理维持了SGC-7901细胞的增殖。
线粒体KATP开放受损导致MMP丧失，并参与姜黄素诱导的胃癌细胞凋亡。
