Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma is associated with increased autocrine of IGF1.
Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma is associated with increased autocrine of IGF1.
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DOI：
10.1371/journal.pone.0089686
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Tang ZY
中科院分区：
文献类型：
--
作者：
Bu Y;Jia QA;Ren ZG;Zhang JB;Jiang XM;Liang L;Xue TC;Zhang QB;Wang YH;Zhang L;Xie XY;Tang ZY
证据表明，许多类型的癌症是由不同类型的细胞组成的，包括癌症干细胞（CSCs）。我们之前已经表明，化疗药物奥沙利铂诱导上皮-间质转化，这被认为是生成CSCs的重要机制。在本研究中，我们研究奥沙利铂治疗的癌症组织是否具有CSCs的特征，并探讨这些组织中奥沙利铂的耐药性。将肝癌细胞（MHCC97H细胞）皮下注射到小鼠体内形成肿瘤，并用奥沙利铂或葡萄糖静脉治疗小鼠。五周后，将肿瘤原位移植到其他小鼠的肝脏中，并用奥沙利铂或葡萄糖治疗这些小鼠。评估转移潜能、对奥沙利铂的敏感性和异种移植肿瘤组织中csc相关标志物的表达。DNA微阵列用于测量奥沙利铂治疗后基因表达的变化。此外，建立了奥沙利铂耐药细胞系（MHCC97H-OXA），以评估胰岛素样生长因子1分泌、细胞侵袭、细胞集落形成、奥沙利铂敏感性和csc相关标志物的表达。还评估了胰岛素样生长因子1受体抑制剂的作用。奥沙利铂治疗抑制皮下肿瘤生长。奥沙利铂治疗小鼠的肿瘤随后异种移植到其他小鼠的肝脏中，表现出对奥沙利铂敏感性降低和肺转移潜力增加。在csc相关蛋白的表达中，胰岛素样生长因子1基因在这些肿瘤组织中表达上调。此外，MHCC97H-OXA细胞显示增加细胞侵袭、集落形成和胰岛素样生长因子1和csc相关标记物的表达，而胰岛素样生长因子1受体抑制剂抑制了这些作用。奥沙利铂耐药肝癌细胞的干细胞维持与IGF1的自分泌增加有关。
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. 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. 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. Maintenance of stemness in oxaliplatin-resistant hepatocellular carcinoma cells is associated with increased autocrine of IGF1.
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DOI：
10.1155/2012/908601
发表时间：
2012
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Jia QA;Ren ZG;Bu Y;Wang ZM;Zhang QB;Liang L;Jiang XM;Zhang QB;Tang ZY
通讯作者：
Tang ZY
影响因子：
13.5
作者：
Lee, Terence Kin Wah;Castilho, Antonia;Ng, Irene Oi Lin
通讯作者：
Ng, Irene Oi Lin
影响因子：
11.5
作者：
Chitnis, Meenali M.;Yuen, John S. P.;Macaulay, Valentine M.
通讯作者：
Macaulay, Valentine M.
影响因子：
11.5
作者：
Adhami, Vaqar Mustafa;Afaq, Farrukh;Mukhtar, Hasan
通讯作者：
Mukhtar, Hasan
影响因子：
11.5
作者：
Plymate, Stephen R.;Haugk, Kathy;Wu, Jennifer D.
通讯作者：
Wu, Jennifer D.