Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma is associated with increased autocrine of IGF1.
BACKGROUND: Evidence suggests that many types of cancers are composed of different cell types, including cancer stem cells (CSCs). We have previously shown that the chemotherapeutic agent oxaliplatin induced epithelial-mesenchymal transition, which is thought to be an important mechanism for generat...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3954560?pdf=render |
| _version_ | 1811232649071558656 |
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| author | Yang Bu Qing-An Jia Zheng-Gang Ren Ju-Bo Zhang Xue-Mei Jiang Lei Liang Tong-Chun Xue Quan-Bao Zhang Yan-Hong Wang Lan Zhang Xiao-Ying Xie Zhao-You Tang |
| author_facet | Yang Bu Qing-An Jia Zheng-Gang Ren Ju-Bo Zhang Xue-Mei Jiang Lei Liang Tong-Chun Xue Quan-Bao Zhang Yan-Hong Wang Lan Zhang Xiao-Ying Xie Zhao-You Tang |
| author_sort | Yang Bu |
| collection | DOAJ |
| description | BACKGROUND: Evidence suggests that many types of cancers are composed of different cell types, including cancer stem cells (CSCs). We have previously shown that the chemotherapeutic agent oxaliplatin induced epithelial-mesenchymal transition, which is thought to be an important mechanism for generating CSCs. In the present study, we investigate whether oxaliplatin-treated cancer tissues possess characteristics of CSCs, and explore oxaliplatin resistance in these tissues. METHODS: Hepatocellular carcinoma cells (MHCC97H cells) were subcutaneously injected into mice to form tumors, and the mice were intravenously treated with either oxaliplatin or glucose. Five weeks later, the tumors were orthotopically xenografted into livers of other mice, and these mice were treated with either oxaliplatin or glucose. Metastatic potential, sensitivity to oxaliplatin, and expression of CSC-related markers in the xenografted tumor tissues were evaluated. DNA microarrays were used to measure changes in gene expression as a result of oxaliplatin treatment. Additionally, an oxaliplatin-resistant cell line (MHCC97H-OXA) was established to assess insulin-like growth factor 1 secretion, cell invasion, cell colony formation, oxaliplatin sensitivity, and expression of CSC-related markers. The effects of an insulin-like growth factor 1 receptor inhibitor were also assessed. RESULTS: Oxaliplatin treatment inhibited subcutaneous tumor growth. Tumors from oxaliplatin-treated mice that were subsequently xenografted into livers of other mice exhibited that decreasing sensitivity to oxaliplatin and increasing pulmonary metastatic potential. Among the expression of CSC-related proteins, the gene for insulin-like growth factor 1, was up-regulated expecially in these tumor tissues. Additionally, MHCC97H-OXA cells demonstrated that increasing cell invasion, colony formation, and expression of insulin-like growth factor 1 and CSC-related markers, whereas treatment with an inhibitor of the insulin-like growth factor 1 receptor suppressed these effects. CONCLUSION: Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma cells is associated with increased autocrine of IGF1. |
| first_indexed | 2024-04-12T11:06:35Z |
| format | Article |
| id | doaj.art-3cb5ea61f85e4f8694b3427a9c1afdd1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T11:06:35Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3cb5ea61f85e4f8694b3427a9c1afdd12022-12-22T03:35:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e8968610.1371/journal.pone.0089686Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma is associated with increased autocrine of IGF1.Yang BuQing-An JiaZheng-Gang RenJu-Bo ZhangXue-Mei JiangLei LiangTong-Chun XueQuan-Bao ZhangYan-Hong WangLan ZhangXiao-Ying XieZhao-You TangBACKGROUND: Evidence suggests that many types of cancers are composed of different cell types, including cancer stem cells (CSCs). We have previously shown that the chemotherapeutic agent oxaliplatin induced epithelial-mesenchymal transition, which is thought to be an important mechanism for generating CSCs. In the present study, we investigate whether oxaliplatin-treated cancer tissues possess characteristics of CSCs, and explore oxaliplatin resistance in these tissues. METHODS: Hepatocellular carcinoma cells (MHCC97H cells) were subcutaneously injected into mice to form tumors, and the mice were intravenously treated with either oxaliplatin or glucose. Five weeks later, the tumors were orthotopically xenografted into livers of other mice, and these mice were treated with either oxaliplatin or glucose. Metastatic potential, sensitivity to oxaliplatin, and expression of CSC-related markers in the xenografted tumor tissues were evaluated. DNA microarrays were used to measure changes in gene expression as a result of oxaliplatin treatment. Additionally, an oxaliplatin-resistant cell line (MHCC97H-OXA) was established to assess insulin-like growth factor 1 secretion, cell invasion, cell colony formation, oxaliplatin sensitivity, and expression of CSC-related markers. The effects of an insulin-like growth factor 1 receptor inhibitor were also assessed. RESULTS: Oxaliplatin treatment inhibited subcutaneous tumor growth. Tumors from oxaliplatin-treated mice that were subsequently xenografted into livers of other mice exhibited that decreasing sensitivity to oxaliplatin and increasing pulmonary metastatic potential. Among the expression of CSC-related proteins, the gene for insulin-like growth factor 1, was up-regulated expecially in these tumor tissues. Additionally, MHCC97H-OXA cells demonstrated that increasing cell invasion, colony formation, and expression of insulin-like growth factor 1 and CSC-related markers, whereas treatment with an inhibitor of the insulin-like growth factor 1 receptor suppressed these effects. CONCLUSION: Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma cells is associated with increased autocrine of IGF1.http://europepmc.org/articles/PMC3954560?pdf=render |
| spellingShingle | Yang Bu Qing-An Jia Zheng-Gang Ren Ju-Bo Zhang Xue-Mei Jiang Lei Liang Tong-Chun Xue Quan-Bao Zhang Yan-Hong Wang Lan Zhang Xiao-Ying Xie Zhao-You Tang Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma is associated with increased autocrine of IGF1. PLoS ONE |
| title | Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma is associated with increased autocrine of IGF1. |
| title_full | Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma is associated with increased autocrine of IGF1. |
| title_fullStr | Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma is associated with increased autocrine of IGF1. |
| title_full_unstemmed | Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma is associated with increased autocrine of IGF1. |
| title_short | Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma is associated with increased autocrine of IGF1. |
| title_sort | maintenance of stemness in oxaliplatin resistant hepatocellular carcinoma is associated with increased autocrine of igf1 |
| url | http://europepmc.org/articles/PMC3954560?pdf=render |
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