Metronomic gemcitabine targeted tumor vascular microenvironment decreases the population of CD133(+) cells in hepatocarcinoma xenografts.
Metronomic gemcitabine targeted tumor vascular microenvironment decreases the population of CD133(+) cells in hepatocarcinoma xenografts.
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DOI：
10.3233/cbm-140419
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发表时间：
2014
期刊：
影响因子：
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通讯作者：
Shan-Yong Yi;Jing Ruan;Ling Zhao;Y. Ke;Xiangnan Li
中科院分区：
文献类型：
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作者：
Shan-Yong Yi;Jing Ruan;Ling Zhao;Y. Ke;Xiangnan Li
最近，令人信服的证据表明，癌症干细胞样细胞（CSLC）被认为是许多类型的癌症的起始和传播的关键。大多数CSLC依赖于促进其长期生长和自我更新的血管微环境。然而，目前尚不清楚当我们破坏他们的血管微环境时，CSLC是否会被消除。考虑到这些可能性，我们研究了不同化疗方案对肝癌异种移植模型CSLC群体的影响。用不同的治疗方案治疗小鼠肝癌模型：低剂量节拍（LDM）方案，Bolus剂量和低剂量节拍方案的联合治疗，为了比较，使用吉西他滨（GEM）的最大耐受剂量（MTD）化疗的常规细胞毒性方案。所有疗法均产生显著的肿瘤生长延迟。LDM GEM和推注+LDM GEM显著缩小肿瘤球，而MTD GEM对肿瘤球无影响。此外，Bolus+LDM GEM可以更显著地降低CSLC的数量和活内皮祖细胞（EPC）的水平。总体而言，我们的数据表明，推注+LDM GEM是一种有效的治疗方案，可抑制血管生成，攻击肿瘤血管微环境，并减少CSLC的数量。靶向CSLC独特的微环境可能是有效治疗癌症的关键，并显示出巨大的临床应用前景。
Recently, compelling evidence shows that cancer stem-like cells (CSLC) are thought to be critical for initiation and propagation of many types of cancers. Most of CSLC are dependent upon the vascular microenvironments that promote their long-term growth and self-renewal. However, it is not known if when we disrupted their vascular microenvironments, CSLC would be eliminated. Considering these possibilities, we have investigated the influence of different chemotherapy regimens on the CSLC population of hepatocarcinoma xenografts model. The mouse models of hepatocarcinoma were treated with different therapeutic regimens: low-dose metronomic (LDM) regimens, combination therapies of Bolus dose and low-dose metronomic regimens, for the purpose of comparison, a conventional cytotoxic schedule of maximum tolerated dose (MTD) chemotherapy using gemcitabine (GEM). All therapies produced a significant tumor growth delay. LDM GEM and Bolus+LDM GEM significantly reduced the tumor spheres, whereas MTD GEM had no effect on the tumor spheres. Furthermore, Bolus+LDM GEM could more significantly decrease both the population of CSLC and the levels of viable endothelial progenitor cells (EPC). Overall, our data indicate that Bolus+LDM GEM is a potent treatment regimen for inhibiting angiogenesis, attacking the tumor vascular microenvironments, and decreasing the population of CSLC. Targeting the unique microenvironment of CSLC may be the key to effective cancer therapy, and shows great promise for the clinical practice.