کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6481824 1401493 2016 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Gemcitabine treatment promotes pancreatic cancer stemness through the Nox/ROS/NF-κB/STAT3 signaling cascade
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Gemcitabine treatment promotes pancreatic cancer stemness through the Nox/ROS/NF-κB/STAT3 signaling cascade
چکیده انگلیسی


- A new mechanism for gemcitabine resistance via stemness induction is proposed.
- Gemcitabine induces pancreatic CSCs and stemness-associated genes.
- Gemcitabine enhances cell migration, chemoresistance, and tumorigenesis.
- STAT3 pathway partially mediates gemcitabine-induced CSC properties and tumor relapse.
- Nox/ROS/NF-κB participates in gemcitabine-induced STAT3 activation and stemness.

Gemcitabine, the standard chemotherapy drug for advanced pancreatic cancer, has shown limited benefits because of profound chemoresistance. However, the mechanism involved remains unclear. Cancer stem cells exhibit great tumorigenicity and are closely correlated with drug resistance and tumor relapse. In this study, we demonstrated that certain doses of gemcitabine increased the ratios of CD24+ and CD133+ cells and the expression of stemness-associated genes such as Bmi1, Nanog, and Sox2. The enhancement of stemness after gemcitabine treatment was accompanied by increased cell migration, chemoresistance, and tumorigenesis. Moreover, we found that gemcitabine promoted the binding of phosphorylated STAT3 to the promoter of Bmi1, Nanog, and Sox2 genes. Furthermore, inhibition of STAT3 partially reversed gemcitabine-induced sphere formation, migration, chemoresistance, and tumor relapse. We also demonstrated that the activation of STAT3 and gemcitabine-enhanced stemness was NADPH oxidase (Nox)-generated, ROS-dependent, and NF-κB partially mediated the process. Together, our results suggest a pivotal role of pancreatic cancer stem cells in developing chemoresistance toward gemcitabine treatment through the Nox/ROS/NF-κB/STAT3 signaling pathway. These findings will provide new insight for identifying potential targets that can be used to sensitize pancreatic cancer cells to chemotherapy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Letters - Volume 382, Issue 1, 1 November 2016, Pages 53-63
نویسندگان
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