Abstract
Abstract Calycosin is known for its suppression of breast cancer cell growth. We are the first group to report the effects of calycosin in pancreatic cancer development. Growth inhibition of the human pancreatic cell line MIA PaCa-2 was evaluated by MTT assay. Cell cycle distribution was determined by flow cytometry. Cell migratory activity was investigated by a wound healing assay. Subcutaneous xenografting of MIA PaCa-2 cells was conducted in Balb/C nude mice, while orthotopic inoculation of the mouse Pan01 pancreatic cancer cells was performed in C57BL/6 mice. Our results have shown that calycosin exhibited modest growth inhibition of MIA PaCa-2 cells, together with induction of S phase arrest and restoration of p53. Besides, promotion of both caspase-dependent apoptosis and autophagy implicate that the anticancer mechanism of calycosin strongly rely on programmed cell death. Alternatively, calycosin also inhibited the migration of MIA PaCa-2 cells in line with downregulation of epithelial–mesenchymal transition (EMT) and pro-metastatic biomarkers. The above in vitro benefits of calycosin was confirmed by a significant reduction of tumor mass in the MIA PaCa-2 xenograft. Nevertheless, when we look closely on the in vivo anticancer effect of calycosin in the Pan01 orthotopic mice model, although both attenuation of tumor growth and proapoptotic action were confirmed by histological findings, the tumor tissue expression of Snail, vimentin and CD31 was all elevated, indicating possible promotion of EMT and pro-angiogenic potential of the drug. These controversial findings suggest that calycosin could be an effective anticancer agent by promoting programmed cell death and inhibition of cell proliferation of pancreatic cancer cells, while it may also facilitate metastatic development of tumor, particular at the advanced stages. It would be essential to further dissect the conditions and factors that differentiate the dual actions of calycosin in pancreatic cancer therapy. Citation Format: Zhu Zhang, Joshua KS Ko. Calycosin is a double-edged sword in the treatment of pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2875.
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