Suppression of colorectal cancer metastasis by nigericin through inhibition of epithelial-mesenchymal transition  

作　　者：Hou-Min Zhou Tao-Tao Dong Lin-Lin Wang Bo Feng Hong-Chao Zhao Xiu-Ke Fan Min-Hua Zheng 

机构地区：[1]Department of General Surgery, Ruijin Hospital,School of Medicine, Shanghai Jiaotong University, ShanghaiMinimally Invasive Surgery Center, Shanghai 200025, China [2]Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, ShandongProvince, China [3]Shanghai Institute of Medical Genetics, Shanghai Children＇s Hospital, School of Medicine, Shanghai JiaotongUniversity, Shanghai 200025, China

出　　处：《World Journal of Gastroenterology》2012年第21期2640-2648,共9页世界胃肠病学杂志（英文版）

基　　金：Supported by The National Natural Science Foundation, No.30901424;the Leading Medical Talent Foundation of Shanghai Municipality, No. 10XD1402700

摘　　要：AIM: To evaluate the effect of nigericin on colorectal cancer and to explore its possible mechanism. METHODS: The human colorectal cancer (CRC) cell lines HT29 and SW480 were treated with nigericin or oxaliplatin under the conditions specified. Cell viability assay and invasion and metastasis assay were performed to evaluate the effect of nigericin on CRC cells. Sphereforming assay and soft agar colony-forming assay were implemented to assess the action of nigericin on the cancer stem cell properties of CRC cells undergone epithelial-mesenchymal transition (EMT). RESULTS: Compared with oxaliplatin, nigericin showed more toxicity for the HT29 cell line (IC50, 12.92 ± 0.25 μmol vs 37.68 ± 0.34 μmol). A similar result was also obtained with the SW116 cell line (IC50, 15.86 ± 0.18 μmol vs 41.02 ± 0.23 μmol). A Boyden chamber assay indicated that a significant decrease in the number of HT29 cells migrating through polyvinylidene fluoride membrane was observed in the nigericin-treated group, relative to the vehicle-treated group [11 ± 2 cells per high-power field (HPF) vs 19.33 ± 1.52 cells per HPF, P < 0.05]. Compared to the control group, the numbers of HT29 cells invading through the Matrigel-coated membrane also decreased in the nigericin-treated group (6.66 ± 1.52 cells per HPF vs 14.66 ± 1.52 cells per HPF, P < 0.05). Nigericin also reduced the proportion of CD133+ cells from 83.57% to 63.93%, relative to the control group (P < 0.05). Nigericin decreased the number of spheres relative to the control group (0.14 ± 0.01 vs 0.35 ± 0.01, P < 0.05), while oxaliplatin increased the number of spheres relative to the control group (0.75 ± 0.02 vs 0.35 ± 0.01; P < 0.05). Nigericin also showed a decreased ability to form colonies under anchorage-independent conditions in a standard soft agar assay after 14 d in culture, relative to the control group (1.66 ± 0.57 vs 7 ± 1.15, P < 0.05), whereas the colony numbers were higher in the oxaliplatin group relative to the vehicle-treated controls (14.33 ± 0.57 vAIM： To evaluate the effect of nigericin on colorectal cancer and to explore its possible mechanism. METHODS： The human colorectal cancer （CRC） cell lines HT29 and SW480 were treated with nigericin or oxaliplatin under the conditions specified. Cell viability assay and invasion and metastasis assay were performed to evaluate the effect of nigericin on CRC cells. Sphereforming assay and soft agar colony-forming assay were implemented to assess the action of nigericin on the cancer stem cell properties of CRC cells undergone epithelial-mesenchymal transition （EMT）. RESULTS： Compared with oxaliplatin, nigericin showed more toxicity for the HT29 cell line （IC50, 12.92 ± 0.25 μmol vs 37.68 ± 0.34 μmol）. A similar result was also obtained with the SW116 cell line （IC50, 15.86 ± 0.18 μmol vs 41.02 ± 0.23 μmol）. A Boyden chamber assay indicated that a significant decrease in the number of HT29 cells migrating through polyvinylidene fluoride membrane was observed in the nigericin-treated group, relative to the vehicle-treated group [11 ± 2 cells per high-power field （HPF） vs 19.33 ± 1.52 cells per HPF, P 〈 0.05]. Compared to the control group, the numbers of HT29 cells invading through the Matrigel-coated membrane also decreased in the nigericin-treated group （6.66 ± 1.52 cells per HPF vs 14.66 ± 1.52 cells per HPF, P 〈 0.05）. Nigericin also reduced the proportion of CD133＋ cells from 83.57% to 63.93%, relative to the control group （P 〈 0.05）. Nigericin decreased the number of spheres relative to the control group （0.14 ± 0.01 vs 0.35 ± 0.01, P 〈 0.05）, while oxaliplatin increased the number of spheres relative to the control group （0.75 ± 0.02 vs 0.35 ± 0.01; P 〈 0.05）. Nigericin also showed a decreased ability to form colonies under anchorage-independent conditions in a standard soft agar assay after 14 d in culture, relative to the control group （1.66 ± 0.57 vs 7 ± 1.15, P 〈 0.05）, whereas the colony numbers were higher in the oxaliplatin gro

关 键 词：Colorectal cancer  Nigericin  Cancer invasion  Metastasis  Epithelial-mesenchymal transition  CD133  E-cadherin  Vimentin 

分 类 号：Q939.139[生物学—微生物学] TQ465.92[化学工程—制药化工]