PP 49. PKD Inhibitor Has Therapeutic Possibility of Gastric Cancer

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K. Tsuboi, Y. Matsuo, T. Shamoto, T. Shibata, M. Morimoto, T. Wakasugi, H. Ishiguro, M. Kimura, H. Takeyama

18:34 - 18:40h at Lanchid Room

Categories: Poster Session , Surgical Oncology

Session: Poster (P4) - Surgical Oncology

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Background
Angiogenesis is one of the carcinogenesis factors in gastric cancer. IL-8 and VEGF are reported to promote tumor angiogenesis. Protein kinase D (PKD) regulates multiple normal and abnormal biological processes, for example, proliferation, inflammation and angiogenesis. We examined the effects of PKD inhibitor in gastric cancer angiogenesis.

Material and Methods
We used the gastric cancer cell line, MKN45. MKN45 was cultured with phorbol myristate acetate (PMA) that is the inducer of PKD phosphorylation. CID755673 was reported to act as an inhibitor of PKD. The phosphorylation of PKD was estimated by Western blotting. The mRNA expressions of IL-8 were measured by realtime RT-PCR. The secretion levels of IL-8 were measured by ELISA. The tumor angiogenesis of gastric cancer was examined by in vitro angiogenesis assay kit.

Result
In Western blotting, PMA induced PKD phosphorylation on Ser 744 and Ser 916 in MKN45. The induced PKD phosphorylation was decreased by the addition of CID755673. PMA increased mRNA expressions of IL-8 in gastric cancer and CID755673 abrogated the effects. The secretion levels of IL-8 in MKN45 were also increased by PMA and the increased secretion levels were inhibited by CID755673. The tube formation of human umbilical vein endothelial cell (HUVEC) was increased by coculture with MKN45 in vitro angiogenesis assay, and CID755673 decreased the tube formation of HUVEC.

Conclusion
CID755673 inhibited the PMA induced PKD phosphorylation and IL-8 secretion levels in MKN45. PKD inhibitor regressed angiogenesis in gastric cancer. Therefore PKD inhibitor may have an antitumor property in gastric cancer.