Journal
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume 49, Issue 4, Pages 1704-1712Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2016.3670
Keywords
2,3,5,6-tetramethylpyrazine; NKG2D; MICA/B; clear cell renal cell carcinoma; epithelial-mesenchymal transition
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Funding
- Central Research Laboratory, Second Hospital of Shandong University
- National Natural Science Foundation of China [81500042]
- Natural Science Foundation of Shandong Province [ZR2014HQ045, ZR2013HM103]
- Medical and Health Science Technology Development Plan Project of Shandong Province [2015WS0307]
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Tetramethypyrazine (TMP), one of the active compounds extracted from the traditional Chinese medicinal herb (Chuanxiong), has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms have not been fully elucidated. In the present study, the anticancer efficacy of TMP was investigated in human clear cell renal cell carcinoma (ccRCC) cells. We showed that TMP significantly inhibited ccRCC cell viability, proliferation, apoptosis, invasion and migration through the methods of MTT, flow cytometry, wound healing and Transwell assays. Furthermore, reverse transcription polymerase chain reaction (RT-PCR), western blotting and immunofluorescence results demonstrated TMP upregulation of the expression of NKG2D ligands (NKG2DLs) MHC class I chain-related molecules A and B (MICA/B) and epithelial cell expression marker of E-cadherin, and downregulation of mesenchymal cell expression markers of vimentin and fibronectin. Taken together, the inhibition of TMP on ccRCC cells might be mediated via inhibition of NKG2D related signaling pathway to further suppress epithelial-mesenchymal transition (EMT) progression. The binding of NKG2D to its ligands activates NK cells, giving the rationale for studies on the utilization of TMP as a potential cancer therapeutic compound to increase NK cells-mediated cytotoxicity against high MICA/B expression in cancer cells.
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