Latexin inhibits the proliferation of CD133+ miapaca-2 pancreatic cancer stem-like cells.
Latexin inhibits the proliferation of CD133+ miapaca-2 pancreatic cancer stem-like cells.
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乳胶蛋白抑制CD133+ Miapaca-2胰腺癌干细胞的增殖。
DOI：
10.1186/1477-7819-12-404
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发表时间：
2014-12-30
影响因子：
3.2
通讯作者：
Cai ZZ
中科院分区：
文献类型：
--
作者：
Xue ZX;Zheng JH;Zheng ZQ;Cai JL;Ye XH;Wang C;Sun WJ;Zhou X;Lu MD;Li PH;Cai ZZ
越来越多的证据表明胰腺癌中含有肿瘤干细胞(CSCs)，这可能与化疗抵抗有关。Latexin(LXN)是干细胞增殖的负调控因子，我们研究了LXN对CD133+胰腺癌干细胞样细胞的影响。以人胰腺癌细胞系CD133+miapaca-2为研究对象，采用磁激活细胞分选法和流式细胞术对CD133+miapaca-2细胞进行分离。通过漂浮球实验和肿瘤移植实验检测CD133+miapaca-2细胞的自我更新能力、增殖能力和致瘤性。用Western blotting和qRT-PCR分别检测CD133+和CD133-miapaca-2细胞中LXN蛋白和mRNA的表达。CD133+miapaca-2细胞在无血清培养液中加入LXN后，用细胞计数试剂盒8(CCK-8)检测细胞增殖，用流式细胞仪检测细胞凋亡率。检测Bcl2、Bax、c myc蛋白和mRNA的表达水平。我们成功地分离出CD133+miapaca-2细胞，该细胞在SFM中具有自我更新的能力，在DMEM+FBS中具有增殖能力，在裸鼠体内具有高致瘤性。CD133+miapaca-2细胞的LXN蛋白和mRNA表达水平明显低于CD133-细胞。LXN处理CD133+miapaca-2细胞后，细胞凋亡率增加，增殖活性降低，Bcl2和c-myc表达下调，Bax表达上调，呈剂量依赖关系。LXN可诱导CD133+miapaca-2细胞凋亡并抑制其增殖。这些变化与Bcl2、c-myc的下调和Bax的上调有关。
An increasing number of evidence suggests that pancreatic cancer contains cancer stem cells (CSCs), which may be relevant to the resistance of chemotherapy. Latexin (Lxn) is a negative regulator of stem cell proliferation and we investigate the effects of Lxn on CD133+ pancreatic cancer stem-like cells. CD133+ miapaca-2 cells, a human pancreatic carcinoma cell line, were isolated and sorted by magnetic activated cell sorting and flow cytometry. The capacity for self-renewal, proliferation, and tumorigenicity of CD133+ miapaca-2 cells was determined by the floating spheres test and tumor xenograft assays. Protein and mRNA expression of Lxn in CD133+ and CD133- miapaca-2 cells were detected by Western blotting and qRT-PCR, respectively. After CD133+ miapaca-2 cells were treated with Lxn in serum-free medium (SFM), cell proliferation was assayed with a Cell Counting Kit 8 (CCK-8) and apoptosis was analyzed by flow cytometry. The protein and mRNA expression levels of Bcl-2, bax, and c-myc were also analyzed. We successfully isolated CD133+ miapaca-2 cells that exhibited the capacity for self-renewal in SFM, a proliferation potential in DMEM supplemented with FBS, and high tumorigenicity in nude mice. Lxn protein and mRNA expression levels in CD133+ miapaca-2 cells were significantly lower than those in CD133- cells. Lxn-treated CD133+ miapaca-2 cells exhibited increased apoptosis and low proliferation activity, down-regulation of Bcl-2 and c-myc expression, and up-regulation of Bax expression in a dose-dependent manner. Lxn induces apoptosis and inhibits the proliferation of CD133+ miapaca-2 cells. These changes are associated with down-regulation of Bcl-2 and c-myc and up-regulation of Bax.
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DOI：
10.1158/1078-0432.ccr-13-2947
发表时间：
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期刊：
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