Yu Dandan, Zhong Yali, Li Xiaoran, Li Yaqing, Li Xiaoli, Cao Jing, Fan Huijie, Yuan Yuan, Ji Zhenyu, Qiao Baoping, Wen Jian-Guo, Zhang Mingzhi, Kvalheim Gunnar, Nesland Jahn M, Suo Zhenhe
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan, China.
Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway.
Oncotarget. 2015 Dec 15;6(40):42687-703. doi: 10.18632/oncotarget.5883.
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.
癌症干细胞(CSCs)与癌症复发和转移相关。前列腺癌细胞常转移至骨,其细胞因子微环境复杂,有利于细胞存活。在本研究中,体外探究了包括白细胞介素-3(IL-3)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、白细胞介素-11(IL-11)和白细胞介素-24(IL-24)在内的一组白细胞介素对人前列腺癌细胞系LNCaP和PC-3细胞干性的影响。应用磺酰罗丹明B(SRB)和5-乙炔基-2'-脱氧尿苷(EdU)检测来检查对细胞增殖的影响,采用伤口愈合实验和Transwell实验进行迁移和侵袭研究,此外还进行集落形成实验、蛋白质免疫印迹法以及流式细胞术检测干性因子表达和化疗敏感性。我们观察到,IL-3、IL-6和IL-11促进而IL-10和IL-24抑制这两种细胞系的生长、侵袭和迁移。有趣的是,IL-3、IL-6和IL-11显著促进集落形成,并增加两种前列腺癌细胞系中SOX2、CD44和ABCG2的表达。然而,IL-10和IL-24对这些因子的表达表现出相反的作用。与上述发现一致,用IL-3或IL-6或IL-11处理会降低对多西他赛的化疗敏感性,而用IL-10或IL-24处理则会增加多西他赛化疗的敏感性。总之,我们的结果表明,在体外前列腺癌细胞系PC-3和LNCaP中,IL-3、IL-6和IL-11起到肿瘤促进作用而IL-10和IL-24起到肿瘤抑制作用,并且这种差异可能归因于它们对前列腺癌细胞干性的不同影响。