Upregulation of IL-6 is involved in moderate hyperthermia induced proliferation and invasion of hepatocellular carcinoma cells
Upregulation of IL-6 is involved in moderate hyperthermia induced proliferation and invasion of hepatocellular carcinoma cells
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DOI：
10.1016/j.ejphar.2018.06.014
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发表时间：
2018-08-15
影响因子：
5
通讯作者：
Kuang, Dong-Lin
中科院分区：
文献类型：
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作者：
Duan, Xu-Hua;Li, Hao;Kuang, Dong-Lin
越来越多的证据表明，射频消融(RFA)不足反而会促进肿瘤的侵袭和转移过程，而适度热疗对肿瘤进展的影响尚未得到很好的阐明。本研究证实，中温处理可促进肝细胞癌细胞的增殖、迁移和侵袭，其结果表明，中温处理可诱导增殖细胞核抗原和基质金属蛋白酶-2的表达上调。细胞研究表明，中温处理可增加肝癌细胞IL-6、IL-10的mRNA和蛋白表达，而对IL-2、IL-4、IL-8、IL-22、血管内皮生长因子、转化生长因子-β和肿瘤坏死因子-α的表达无明显影响。IL-6的沉默，而不是IL-10的沉默，减弱了适度热疗诱导的增殖和细胞侵袭。此外，我们的数据显示，抑制了核因子-KB，而不是ERK1/2或PI3K/Akt，取消了中等温度处理诱导的IL-6的产生。综上所述，我们的数据表明，核因子-kappa B/IL-6的激活参与了中度高温治疗诱导的肝细胞癌的进展。
Increasing evidences suggested that insufficient radiofrequency ablation (RFA) can paradoxically promote tumor invasion and metastatic processes, while the effects of moderate hyperthermia on cancer progression are not well illustrated. Our present study confirmed moderate hyperthermia treatment can promote the proliferation, migration and invasion of hepatocellular carcinoma (HCC) cells, which was evidenced by the results that moderate hyperthermia induced up regulation of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2). Cellular studies indicated that moderate hyperthermia treatment can increase the mRNA and protein expression of IL-6 and IL-10, while not IL-2, IL-4, IL-8, IL-22, VEGF, TGF-beta, or TNF-alpha, in HCC cells. Silencing of IL-6, while not IL-10, attenuated moderate hyperthermia treatment induced proliferation and cell invasion. Furthermore, our data revealed the inhibition of NF-KB, while not ERK1/2 or PI3K/Akt, abolished moderate hyperthermia treatment induced production of IL-6. Collectively, our data showed that activation of NF-kappa B/IL-6 is involved in moderate hyperthermia treatment induced progression of HCC cells.