LPLUNC1 suppresses IL-6-induced nasopharyngeal carcinoma cell proliferation via inhibiting the Stat3 activation
LPLUNC1 suppresses IL-6-induced nasopharyngeal carcinoma cell proliferation via inhibiting the Stat3 activation
复制标题
LPLUNC1通过抑制Stat3激活抑制IL-6诱导的鼻咽癌细胞增殖
DOI：
10.1038/onc.2013.161
复制
发表时间：
2014-04-17
期刊：
影响因子：
8
通讯作者：
Li, G.
中科院分区：
文献类型：
--
作者：
Liao, Q.;Zeng, Z.;Li, G.
Tumor-associated macrophage (TAM)-related chronic inflammation and interleukin-6 (IL-6) contribute to the progression of nasopharyngeal carcinoma (NPC). In this study, we characterized TAMs and IL-6 expression in 212 biopsied NPC and 119 non-tumor nasopharyngeal epithelium (NPE) tissues by tissue array. In comparison with that in the NPE tissues, more TAM infiltrates and a higher density of IL-6 expression were detected in NPC tissues, which were associated with the poor survival of NPC patients. In contrast, little or no LPLUNC1, a regulator of inflammation, expression was detected in NPC tissues, and the levels of LPLUNC1 expression in the NPC were associated negatively with the numbers of TAMs and the levels of IL-6 expression, but positively with the survival of NPC patients. Induction of LPLUNC1 overexpression in NPC cells mitigated lipopolysaccharide (LPS)-induced IL-6, IL-8, tumor necrosis factor-α and IL-1β expression or treatment of THP-1 macrophages with LPLUNC1 inhibited spontaneous and LPS-induced IL-6 expression in vitro. IL-6-promoted NPC cell proliferation in a dose-and time-dependent manner, accompanied by increasing cyclin D1 and Bcl-2 expression and the Stat3 activation, but inhibiting Bax and p21 expression. Induction of LPLUNC1 overexpression inhibited NPC cell proliferation, induced NPC cell arrest, promoted NPC cell apoptosis even after IL-6 stimulation and inhibited the growth of implanted NPC tumors in vivo, which were associated with decreasing cyclin D1 and Bcl-2 expression and the Janus kinase 2 (JAK2)/Stat3 activation, but enhancing Bax and p21 expression. These results suggest that LPLUNC1 can inhibit inflammation and NPC growth by downregulating the Stat3 pathway.
