This study is to investigate whether naked plasmid
DNA can effectively transfect
lung cancer related cells and express human
kallistatin, an endogenous
protein that inhibits angiogenesis and
tumor growth, and to explore the
biological activity of the low-level expressed
kallistatin to
lung cancer in vitro and in vivo. The plasmids were delivered with
Lipofectamine 2000 to transfect various
lung cancer related cells. Kal expression was determined by ELISA. The
biological effects of Kal expression on proliferation, migration and apoptosis rate of the cells were examined. In subcutaneous NCI-H446 xenograft model, pKal was injected directly into
tumors, the changes of CD34, Ki-67 and
E-cadherin expression were detected with immunohistochemical assay, the
tumor apoptosis was analyzed with TUNEL assay. Both the endothelial cell and
lung cancer cells could express
kallistatin after plasmid transfection. The proliferation and migration of human umbilical vein endothelial cells were inhibited, but the apoptosis rate was not affected. The proliferation rates of all the three tested
lung cancer cells, such as NCI-H446, NCI-H460 and A549, were inhibited, and their apoptosis rates were enhanced, but different cells behaved differently. In subcutaneous NCI-H446 xenograft model, intratumor injection of pKal inhibited the growth of
lung cancer by reducing angiogenesis and proliferation of
tumor cells. In conclusion, this study demonstrated the efficacy of plasmid-mediated expression of
kallistatin to
lung cancer related cells, thus providing a basis for their clinical application in the treatment of
lung cancer.