STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells.
STAT3 as a potential therapeutic target in ALDH+ and CD44+/CD24+ stem cell-like pancreatic cancer cells.
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STAT3 作为 ALDH 和 CD44 /CD24 干细胞样胰腺癌细胞的潜在治疗靶点。
DOI：
10.3892/ijo.2016.3728
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发表时间：
2016-12
影响因子：
5.2
通讯作者：
Lin J
中科院分区：
文献类型：
--
作者：
Lin L;Jou D;Wang Y;Ma H;Liu T;Fuchs J;Li PK;Lü J;Li C;Lin J
信号转导和转录激活因子3 （STAT3）的持续激活通常在包括胰腺癌在内的许多类型的癌症中检测到。STAT3是否在干细胞样胰腺癌细胞中被激活以及STAT3抑制的作用尚不清楚。采用流式细胞术分离出醛脱氢酶（ALDH）阳性（ALDH+）和分化簇（CD） 44阳性/CD24阳性亚群（CD44+/CD24+）鉴定的胰腺癌干细胞样细胞。研究STAT3在ALDH+和CD44+/CD24+细胞中的活化作用以及STAT3抑制剂、ll12、FLLL32和statstatic对STAT3的抑制作用。我们的研究结果表明，与ALDH阴性（ALDH−）和CD44阴性/CD24阴性（CD44−/CD24−）胰腺癌细胞相比，ALDH+和CD44+/CD24+胰腺癌干细胞样细胞表达了更高水平的磷酸化STAT3，这是STAT3的一种活性形式，表明STAT3在胰腺癌干细胞样细胞中被激活。小分子STAT3抑制剂抑制ALDH+和CD44+/CD24+细胞中STAT3磷酸化、STAT3下游靶基因表达、细胞活力和肿瘤球形成。我们的研究结果表明，STAT3是胰腺癌干细胞样细胞的一个新的治疗靶点，通过STAT3抑制剂抑制这些细胞中活化的STAT3可能提供一种有效的胰腺癌治疗方法。
Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer including pancreatic cancer. Whether STAT3 is activated in stem cell-like pancreatic cancer cells and the effect of STAT3 inhibition, is still unknown. Flow cytometry was used to isolate pancreatic cancer stem-like cells which are identified by both aldehyde dehydrogenase (ALDH)-positive (ALDH+) as well as cluster of differentiation (CD) 44-positive/CD24-positive subpopulations (CD44+/CD24+). STAT3 activation and the effects of STAT3 inhibition by STAT3 inhibitors, LLL12, FLLL32, and Stattic in ALDH+ and CD44+/CD24+ cells were examined. Our results showed that ALDH+ and CD44+/CD24+ pancreatic cancer stem-like cells expressed higher levels of phosphorylated STAT3, an active form of STAT3, compared to ALDH-negative (ALDH−) and CD44-negative/CD24-negative (CD44−/CD24−) pancreatic cancer cells, suggesting that STAT3 is activated in pancreatic cancer stem-like cells. Small molecular STAT3 inhibitors inhibited STAT3 phosphorylation, STAT3 downstream target gene expression, cell viability, and tumorsphere formation in ALDH+ and CD44+/CD24+ cells. Our results indicate that STAT3 is a novel therapeutic target in pancreatic cancer stem-like cells and inhibition of activated STAT3 in these cells by STAT3 inhibitors may offer an effective treatment for pancreatic cancer.
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DOI：
10.1186/bcr920
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dontu G;Jackson KW;McNicholas E;Kawamura MJ;Abdallah WM;Wicha MS
通讯作者：
Wicha MS
影响因子：
11.2
作者：
Li, Chenwei;Heidt, David G.;Simeone, Diane M.
通讯作者：
Simeone, Diane M.
影响因子：
50.5
作者：
Paydas, S;Tanriverdi, K;Burgut, R
通讯作者：
Burgut, R
影响因子：
254.7
作者：
Siegel, Rebecca;Naishadham, Deepa;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
10.3
作者：
Sahu, Ravi P.;Srivastava, Sanjay K.
通讯作者：
Srivastava, Sanjay K.