Research Papers:
ILs-3, 6 and 11 increase, but ILs-10 and 24 decrease stemness of human prostate cancer cells in vitro
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Abstract
Dandan Yu1, Yali Zhong1, Xiaoran Li7,8, Yaqing Li1, Xiaoli Li1, Jing Cao1,2, Huijie Fan1, Yuan Yuan3, Zhenyu Ji4, Baoping Qiao5, Jian-Guo Wen5, Mingzhi Zhang1, Gunnar Kvalheim6, Jahn M. Nesland7,8, Zhenhe Suo1,7,8
1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan, China
2Departments of Pathology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
3Department of Pathology, Capital Medical University, Beijing, China
4Department of Oncology, Henan Academy of Medical & Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
5Department of Urodynamic Center and Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan, China
6Department of Cell Therapy, Cancer Institute, Radium Hospital, Oslo University Hospital, Oslo, Norway
7Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
8Department of Pathology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
Correspondence to:
Zhenhe Suo, e-mail: [email protected]
Keywords: interleukin, cytokines, cancer stem cells, chemotherapy, CD44 and ABCG2
Received: June 23, 2015 Accepted: October 09, 2015 Published: October 21, 2015
ABSTRACT
Cancer stem cells (CSCs) are associated with cancer recurrence and metastasis. Prostate cancer cells often metastasize to the bone with a complex microenvironment of cytokines favoring cell survival. In this study, the cell stemness influence of a group of interleukins including IL-3, 6, 10, 11 and 24 on human prostate cancer cell lines LNCaP and PC-3 was explored in vitro. Sulforhodamine B(SRB) and 5-ethynyl-2′-deoxyuridine (EdU) assays were applied to examine the effect on cell proliferation, and wound healing and transwell assays were used for migration and invasion studies, in addition to colony formation, Western blotting and flowcytometry for the expression of stemness factors and chemotherapy sensitivity. We observed that ILs-3, 6 and 11 stimulated while ILs-10 and 24 inhibited the growth, invasion and migration of both cell lines. Interestingly, ILs-3, 6 and 11 significantly promoted colony formation and increased the expression of SOX2, CD44 and ABCG2 in both prostate cancer cell lines. However, ILs-10 and 24 showed the opposite effect on the expression of these factors. In line with the above findings, treatment with either IL-3 or IL-6 or IL-11 decreased the chemosensitivity to docetaxel while treatment with either IL-10 or IL-24 increased the sensitivity of docetaxel chemotherapy. In conclusion, our results suggest that ILs-3, 6 and 11 function as tumor promoters while ILs-10 and 24 function as tumor suppressors in the prostate cancer cell lines PC-3 and LNCaP in vitro, and such differences may attribute to their different effect on the stemness of PCa cells.
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