Study on Indole-3-carbinol inhibits nasopharyngeal carcinoma cells growth in vitra and in vivo
-
摘要: 目的: 研究吲哚-3-甲醇(I3C)在体内和体外实验中对鼻咽癌细胞的抑制作用及其可能的机制。方法: 在体外实验中,以0、100、200、300 μmol/L不同浓度的I3C分别作用于人鼻咽癌CNE2细胞株0、24、48和72 h后,检测细胞增殖能力。检测各浓度I3C处理CNE2细胞株48 h后细胞凋亡率。检测各浓度I3C处理后PI3K/Akt通路相关蛋白PI3K p110α、PI3K p85、p-Akt和p-GSK3-β的表达水平。在体内实验中,将BALB/c裸鼠分为I3C预防组、I3C治疗组和对照组。通过给裸鼠种植肿瘤细胞成瘤,预防组和治疗组的裸鼠均给予含0.5%的I3C的饲料喂养,检测各组裸鼠肿瘤生长情况,8周后检测各组裸鼠肿瘤中PI3K/Akt通路相关蛋白的表达水平。结果: 随着I3C浓度的增加,细胞的增殖能力明显减弱,凋亡率显著增加,PI3K/Akt通路相关蛋白的表达水平降低。在动物实验中,与对照组相比,8周后预防组和治疗组肿瘤体积明显缩小,裸鼠肿瘤中PI3K/Akt通路相关蛋白的表达水平也降低。同时,苏木精-伊红染色检测各组小鼠心、肝、肾组织未见明显变化。结论: I3C可以在体内和体外有效地抑制鼻咽癌细胞的生长,且诱导凋亡,其作用机制可能是抑制PI3K/Akt信号通路。
-
关键词:
- 鼻咽肿瘤 /
- 吲哚-3-甲醇 /
- 细胞凋亡 /
- PI3K/Akt通路
Abstract: Objective: The aim of this study is to investigate the inhibition of nasopharyngeal carcinoma cells by indole-3-carbinol in vitro and in vivo.Method: The human nasopharyngeal carcinoma cell line CNE2 was treated in different concentrations 0,100,200,300 μmol/L of indole-3-carbinol. Then we detected cell proliferation after 0,24,48 and 72 h, apoptosis after 48 h and the levels of PI3K/Akt pathway-related proteins in vitro. The BALB/c nude mice were divided into three groups:prevention group, treatment group and control group. In vivo, the nude mice in every group were inoculated with nasopharyngeal carcinoma cells CNE2, and mice in prevention and treatment groups were given feed containing 0.5% indole-3-carbinol. We investigated the tumoricidal effect of I3C in nude mice, and eight weeks later, the PI3K/Akt pathway-related proteins expressions in tumors from nude mice of each group were detected.Result: With the indole-3-carbinol concentration increased, cell proliferation decreased and apoptosis increased significantly.The levels of PI3K/Akt pathway-related proteins were decreased.In animal experiments, the prevention and treatment group developed smaller tumors, and the expression of PI3K/Akt pathway-related proteins in prevention and treatment groups PI3K/Akt pathway also reduced, compared to control group. Meanwhile, nearly no changes of heart, liver and kidney tissues in all groups were seen in HE staining.Conclusion: Indole-3-carbinol inhibited the growth of nasopharyngeal carcinoma cells and induced apoptosis effectively in vivo and in vitro. The mechanism might be that indole-3-carbinol could suppress PI3K/Akt pathway.-
Key words:
- nasopharyngeal neoplasms /
- indole-3-carbinol /
- apoptosis /
- PI3K/Akt pathway
-
-
[1] CHINNI SR,LI Y,UPADHYAY S,et al.Indole-3-carbinol(I3C)induced cell growth inhibition,G1 cell cycle arrest and apoptosis in prostate cancer cells[J].Oncogene,2001,20:2927-2936.
[2] NACHSHON-KEDMI M,YANNAI S,HAJ A,et al.Indole-3-carbinol and 3,3'-diindolylmethane induce apoptosis in human prostate cancer cells[J].Food Chem Toxicol,2003,41:745-752.
[3] ARONCHIK I,CHEN T,DURKIN KA,et al.Target protein interactions of indole-3-carbinol and the highly potent derivative 1-benzyl-I3C with the C-terminal domain of human elastase uncouples cell cycle arrest from apoptotic signaling[J].Mol Carcinog,2012,51:881-894.
[4] TAYLOR-HARDING B,AGADJANIAN H,NASSANIAN H,et al.Indole-3-carbinol synergistically sensitises ovarian cancer cells to bortezomib treatment[J].Br J Cancer,2012,106:333-343.
[5] AGGARWA B B,ICHIKAWA H.Molecular targets and anticancer potential of indole-3-carbinol and its derivatives[J].Cell Cycle,2005,4:1201-1215.
[6] CHAN Y W,LEE V H,CHOW V L,et al.Extracapsular lymph node spread in recurrent nasopharyngeal carcinoma[J].Laryngoscope,2011,121:2576-2580.
[7] MA B B,CHAN A T.Recent perspectives in the role of chemotherapy in the management of advanced nasopharyngeal carcinoma[J].Cancer,2005,103:22-31.
[8] RAHMAN KM,LI Y,SARKAR F H.Inactivation of akt and NF-kappaB play important roles during indole-3-carbinol-induced apoptosis in breast cancer cells[J].Nutrition and cancer,2004,48:84-94.
[9] WATANABE S,SATO K,OKAZAKI Y,et al.Activation of PI3K-AKT pathway in oral epithelial dysplasia and early cancer of tongue[J].Bull Tokyo Dent Coll,2009,50:125-133.
[10] JONES R G,PARSONS M,BONNARD M,et al.Protein kinase B regulates T lymphocyte survival,nuclear factor kappaB activation,and Bcl-X(L)levels in vivo[J].J Exp Med,2000,191:1721-134.
[11] WU T Y,SAW C L,KHOR T O,et al.In vivo pharmacodynamics of indole-3-carbinol in the inhibition of prostate cancer in transgenic adenocarcinoma of mouse prostate(TRAMP)mice:involvement of Nrf2 and cell cycle/apoptosis signaling pathways[J].Molecular carcinogenesis,2012,51:761-770.
[12] CHEN D Z,QI M,AUBORN K J,et al.Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium[J].J Nutr,2001,131:3294-3302.
[13] WANG Y Q,CHEN C,CHEN Z,et al.Indole-3-carbinol inhibits cell proliferation and induces apoptosis in Hep-2laryngeal cancer cells[J].Oncol Rep,2013,30:227-233.
-
计量
- 文章访问数: 241
- PDF下载数: 116
- 施引文献: 0