Protein kinase Calpha-responsive polymeric carrier: its application for gene delivery into human cancers.
For cancer-targeting gene delivery, we applied a protein kinase C (PKC)alpha-responsive polymeric carrier to human cancers (U-87 MG [human glioblastoma-astrocytoma, epithelial-like cell line] and A549 [human lung adenocarcinoma epithelial cell line]). Two polymers, one a PKCalpha-responsive polymer (PPC[S]) containing the phosphorylation site serine, and the other a negative control polymer (PPC[A]), in which the serine was substituted with alanine, were synthesized. No cytotoxicity of the polymer was identified. When the complexes were transfected into cancer cells or tissues in which PKCalpha was hyper-activated, the luciferase expression from the PPC(S)/plasmid (pDNA) complex was higher than that from the PPC(A)/pDNA complex. These results show that the phosphorylation of complex by PKCalpha in cancer cells leads to high gene expression and that our system can be used as a human cancer cell-targeting gene delivery system.
Tomiyama
Tetsuro
T
Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan.
Kang
Jeong-Hun
JH
Toita
Riki
R
Niidome
Takuro
T
Katayama
Yoshiki
Y
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011108:Polymers / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000235:genetics*; D014162:Transfection
D011108:Polymers; D008156:Luciferases; D051571:Protein Kinase C-alpha