[CaMKIIγ promotes in vitro and in vivo growth of colorectal cancer cells by upregulating nuclear factor-κB signaling pathway].

OBJECTIVE: To investigate the effects of the γ isoform of Ca(2+)/calmodulin-dependent protein kinase II (CaMKIIγ) on colorectal cancer (CRC) cell growth in vitro and in vivo and explore the mechanisms.

METHODS: The mRNA levels of CaMKIIγ in 5 CRC cell lines, tumor tissues and matched adjacent tissues from 20 CRC patients were examined by semi-quantitative RT-PCR. The lentiviral vector pLenti6.3-MCS-IRES2-eGFP was used to generate the lentivirus particle Lenti-CaMKIIγ for transfecting SW620 cells. The proliferation ability of the transfected SW620-CaMKIIγ cells was assessed by growth curve and colony formation assay. The expression of IKKα, IKKβ, IKKγ, p-IKKα/β, p-IκB andIκB of the transfected cells were determined by Western blotting, and the expression and localization of nuclear factor-κB (NF-κB) p65 were detected by immunofluorescence. In nude mouse models bearing the transfected SW620-CaMKIIγ cell xenograft, the tumor volume was measured twice a week.

RESULTS: CaMKIIγ mRNA showed high expressions in the 5 colorectal cancer cell lines. Eighteen of the 20 tumor tissues showed higher expressions of CaMKIIγ than the adjacent non-tumor tissues. The proliferation of transfected SW620-CaMKIIγ cells was enhanced significantly. CaMKIIγ activated NF-κB signaling pathway and led to NF-κB p65 nuclear translocation. In the tumor-bearing mouse model, the volume of the tumors generated by the transfected SW620-CaMKIIγ cells was 1.46- and 1.68-fold higher than that of the tumors with the control cells at the 8th and 12th day, respectively.

CONCLUSION: CaMKIIγ can effectively promote the growth of colorectal cancer cells in vitro and in vivo by activating NF-κB signaling pathway.