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Archive > Volume 22 Issue 6 > 2015,22(6):675-683. DOI:10.3872/j.issn.1007-385X.2015.06.001 Prev Next
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Molecular mechanism of multi-target tyrosine kinase inhibitors-combined with NK cells againest human hepatocellular carcinoma
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Abstract:
There are no standard effective systemic therapies for patients with hepatocellular carcinoma diagnosed at advanced stage, who have poor prognosis. It has been shown that Multi-target tyrosine kinase inhibitors (MTKIs) and adoptive NK cell immunotherapy have synergistic effect on hepatocellular carcinoma cells. In addition to blocking cell proliferation and angiogenesis signal pathway in tumor tissue to promote apoptosis, MTKIs also induce the expression of natural killer group 2 member D ligands (NKG2DLs) on tumor cells, which interact with NKG2D on NK cells to activate their antitumor activity. It is evident that MTKIs act on signaling molecules involved in DNA damage response, leading to activation of the alternative NF-κB complex that consists of NF-κB2 and RelB, which in turn increases the transcription of NKG2DLs. These results provided a mechanistic rationale for therapy using MTKIs together with adoptive NK cell transfer in the treatment of advanced hepatocellular carcinoma.
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Project Supported:
Project supported by the National Natural Science Foundation for Young Scientists of China (No. 81302372，81300431), and the Excellent Middle and Yong Aged Experts Project of Zhujiang Hospital of Southern Medical University（No.201206012)
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