Abstract 197: Astragalus polysaccharides (APS) effects on betel-nuts related head and neck squamous cell carcinoma (HNSCC) in Taiwan

Abstract

Abstract Backgrounds: The treatment of HNSCC in Taiwan is still very challenging and might be related to betel-nuts use. Betel-nuts chewing might contribute to (1)strong inflammation, invasion, and angiogenesis; (2)poor response to chemotherapy , radiation, and epidermal growth factor receptor inhibitors. In our previous studies, betel-nuts related TW2.6(p53 defective mutation, p16 loss, BCL2+) was resistant to traditional chemotherapies, radiation, and EGFR inhibition. In addition to PI3K/mTOR dual inhibition, polo-like kinase inhibitor with radiation, CDK4/6 inhibitor, WEE1 inhibitor, ALK/IGF-1R inhibitor, Bcl2 inhibitor, and eribulin, FGFR inhibitor & VEGFR2/FGFR/PDGFR or VEGFR2/c-MET/Axl triple blockage might be effective on TW2.6 and reverse treatment refractoriness, maybe through the inhibition of mesenchymal transformation & PI3K/Akt/mTOR signaling and the modulation of stemness & PD1/PDL1 pathway. PI3Kalpha inhibitor, Bcl2 inhibitor, and ALK/IGF-1R inhibitor also have roles to reverse treatment refractoriness. Astragalus polysaccharides is a kind of traditional Chinese medicine with immuno-modulatory effects(enhancing mature DC, NK cells, & effector CD8 cytolytic activity; adjusting chronic inflammation in tumor microenvironment; reversing M2 polarization; suppressing Treg/MDSC) and maybe anti-tumor efficacy. APS has also been manufactured to treat cancer-related fatigue in Taiwan. Purpose: We try to find out whether APS has anti-tumor effects on betel-nuts related HNSCC in Taiwan. Methods: APS was tested on TW2.6 to evaluate (1)the in vitro drug sensitivity; (2)synergistic effects with some target therapies by MTT assay, colon formation assay, flow cytometry, and western blot assay; (3) HUVEC response and invasion capacity by wound healing. Results: APS has minimal cytotoxic effect on TW2.6; however, it could inhibit tumor migration, suppress signals of epithelial-mesenchymal transformation & PI3K/AKT/mTOR pathway, and induce PDL1 drop. APS re-sensitizes TW2.6 to respond to afatinib & volasertib and could enhance further response of TW2.6 to BYL719, foretinib, BGJ398, and eribulin. APS and eribulin combinations might drop BMI-1. Conclusions: APS could possibly reverse TW2.6 treatment refractoriness to EGFR inhibitor & polo-like kinase inhibitor and further enhance PI3Kalpha inhibitor, VEGFR/c-MET/Axl triple inhibitor, FGFR inhibitor, & eribulin effects on TW2.6. APS can be further investigated to be combined with these targeted therapies and even immunotherapy in betel-nuts related HNSCC in Taiwan in the future, by modulating EMT, PI3K/AKT/mTOR pathway, immune escape, & cancer stemness. Citation Format: Jo-Pai Chen, Jui-Ying Chang, Sung-Hsin Kuo, Ruey-Long Hong. Astragalus polysaccharides (APS) effects on betel-nuts related head and neck squamous cell carcinoma (HNSCC) in Taiwan [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 197.