MEK inhibitor diminishes nasopharyngeal carcinoma (NPC) cell growth and NPC-induced osteoclastogenesis via modulating CCL2 and CXCL16 expressions
Nasopharyngeal carcinoma (NPC) is a common malignancy in southern China and Southeast Asia. NPC frequently metastasizes to the bone in advanced patients resulting in high mortality. The molecular mechanisms for NPC development and cancer-induced bone lesions are unclear. In this study, we firstly determined chemokine receptor CCR2 and CXCR6 expressions in clinical specimens and CNE2, SUNE1, CNE1, and HK1 cell lines. Then, we measured chemokine CCL2 and CXCL16 production in these NPC cell lines by ELISA. Expression levels of these chemokines and their receptors were observed to positively correlate with tumor aggressiveness. Furthermore, U0126 (MEK inhibitor) was used to treat these NPC cell lines. CCL2 and CXCL16 expression levels and cell proliferation were significantly inhibited by U0126 in a dose- and time-dependent manner. Finally, we collected conditioned medium (CM) from NPC cell cultures in the presence of U0126 treatment. When mouse bone marrow non-adherent cells were treated with the CM, the numbers of multinucleated osteoclast formation were dramatically diminished. These results indicate that MEK inhibitor diminishes NPC cell proliferation and NPC-induced osteoclastogenesis via modulating CCL2 and CXCL16 expressions. This study provides novel therapeutic targets such as CCL2/CCR2 and CXCL16/CXCR6 for advanced NPC patients.
KeywordsCCL2/CCR2 CXCL16/CXCR6 U0126 Osteoclastogenesis Nasopharyngeal carcinoma
This work was supported by grants from the National Natural Science Foundation of China (Nos. 81171993, 81272415, 81130046, 81272340, and 81030043), Guangxi Key Projects (No. 2013GXNSFEA053004), Guangxi Projects (No. 2012GXNSFCB053004), and Guangxi Ministry of Education (Nos. 201202ZD022 and 201201ZD004). The authors thank Dr.. Jiejun Fu for helpful discussions and Ms. Xiaolin Zhou and Ms. Xin Huang for the English editing.
Conflict of interest
- 33.Cook LM, Shay G, Aruajo A, et al. Integrating new discoveries into the “vicious cycle” paradigm of prostate to bone metastases. Cancer Metastasis Rev 2014.Google Scholar