Abstract A22: Targeting S100p Sensitizes Pancreatic Cancer Cells towards Gemcitabine

Abstract

Abstract Introduction: S100P (S100 Calcium Binding Protein P) is a member of S100 family proteins and plays important roles in cancers. S100p is up-regulated in Pancreatic Ductal Adenocarcinoma (PDAC). There is an up-regulation of S100p in pancreatic intraepithelial neoplasia (PanIN) tissue samples as well as a correlation of its expression with the grade of PanIN. S100p interacts with Receptor for Advanced Glycation End product (RAGE), whose downstream signaling pathways MAPK and NF-kB are responsible for the tumor progression and chemo resistance of PDAC. Thus, abrogation of the RAGE activation may be beneficial towards pancreatic cancer treatment. Therefore, we would like to investigate the growth and chemosensitivity of PDAC cells upon silencing S100p. Methodology: The S100p in PDAC cell lines Capan2 and CFPAC1 was knocked down by lentiviral shRNA. Cell growth, wound healing, colonies formation ability and the tumorigenicity of the S100p knocked down cell lines were evaluated. Moreover, the chemosensitivity of PDAC cells with S100p knockdown towards gemcitabine was evaluated with cell viability assay. Result: Knock-down of S100p inhibited PDAC cell growth and cell migration. RNAi targeting S100p in PDAC cells inhibited cell proliferation. Knock-down of S100p inhibited PDAC tumor growth in nude mice. Enhanced sensitization to gemcitabine on PDAC cells with S100p knock-down was also observed. Conclusion: Our findings suggest that silencing S100p not only can inhibit the in vitro and in vivo growth of PDAC, but also can sensitize PDAC towards gemcitabine treatment. Our result provides a promising alternative by targeting S100p in combinatorial chemotherapy development for pancreatic cancer . Financial support: The work described in this paper was supported by grants from the General Research Fund, Research Grants Council of Hong Kong (CUHK462109, CUHK462713 and 14102714), National Natural Science Foundation of China (81101888) and Direct Grant from CUHK to YC. Citation Format: Shing Chun Tang, Yangchao Chen.{Authors}. Targeting S100p Sensitizes Pancreatic Cancer Cells towards Gemcitabine. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A22.