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LPLUNC1 suppresses IL-6-induced nasopharyngeal carcinoma cell proliferation via inhibiting the Stat3 activation

Oncogene volume 33, pages 2098–2109 (2014)Cite this article

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Abstract

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.

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Acknowledgements

This study was supported by grants from the National High Technology Research and Development Program of China (2012AA02A206), the National Natural Science Foundation of China (91229122, 81071644, 81172189, 81101509, 81171930, 81272254 and 81272298), the 111 project (111-2-12), the Program for New Century Excellent Talents in University (NCET-11-0520) and the Hunan Province Natural Sciences Foundation of China (10JJ7003).

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  1. Q Liao and Z Zeng: These authors contributed equally to this work.

Authors and Affiliations

  1. Hunan Provincial Tumor Hospital and the Affiliated Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China

    Q Liao, Z Zeng, X Li, J Ma, M Wu, W Xiong & G Li

  2. Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China

    Q Liao, Z Zeng, X Li, X Li, J Ma, M Wu, W Xiong & G Li

  3. Key Laboratory of Carcinogenesis of Ministry of Health and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China

    Q Liao, Z Zeng, X Guo, X Li, F Wei, W Zhang, P Chen, F Liang, B Xiang, J Ma, M Wu, H Tang, M Deng, X Zeng, K Tang, W Xiong & G Li

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Liao, Q., Zeng, Z., Guo, X. et al. LPLUNC1 suppresses IL-6-induced nasopharyngeal carcinoma cell proliferation via inhibiting the Stat3 activation. Oncogene 33, 2098–2109 (2014). https://doi.org/10.1038/onc.2013.161

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