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Abstract 4199: Resveratrol inducedREG IIIand inhibited head and neck cancer progression

Head and neck squamous cell carcinoma (HNSCC) is one of the 10 most common malignancies in the world and known for clinical progression and poor prognosis. Despite the recent progress of the treatment for improving locoregional control in HNSCC patients, that for recurrence and metastatic control remains insufficient, indicating that there is a continued need for improved treatment strategies. Therefore, the key molecules that enhance chemo- and radio-sensitivity in HNSCC and identification of reliable biomarkers for predicting the recurrence and metastasis would be desirable to improve the prognosis of HNSCC. The human regenerating gene (REG) expression has been reported to be associated with progression of various cancers. Recently, we have reported that REG III expression is associated with an improved survival rate for HNSCC patients as a reliable biomarker. Herein, we investigated the inducer for REG III expression in HNSCC cells and found that resveratrol significantly increased the REG III promoter activity and REG III mRNA. In addition, we demonstrated that the effects of resveratrol on cancer cell progression in HNSCC in vitro and in vivo. To reveal the effects of resveratrol on HNSCC cell proliferation, cell proliferation was measured by using WST-8 assay. Resveratrol significantly inhibited cell growth in FaDu and HSC-4 HNSCC cells. Secondly, to check the effects of resveratrol on chemo- and radio-sensitivity in HNSCC cells, HNSCC cells were expose to cisplatin and radiation, respectively. Resveratrol significantly increased the sensitivity of cisplatin and radiation in HNSCC cells. We also examined the effects of resveratrol on cancer invasion using 24-well Matrigel-coated Transwells. Resveratrol significantly attenuated the cancer invasion of HNSCC cells. Moreover, to assess resveratrol-induced chemo-sensitivity in vivo, we established a xenograft model of HNSCC in BALB/c nude mice. The tumor volumes in the mice receiving combined administration of resveratrol and cisplatin were significantly lower than those of resveratrol or cisplatin alone. These results strongly suggest that resveratrol can inhibit head and neck cancer progression through the REG III expression pathway and can be a potential sensitizer for anticancer therapy for patients with HNSCC. Citation Format: Ichiro Ota, Shinji Mikami, Takashi Masui, Takahiro Kimura, Hirokazu Uemura, Hideyuki Okamoto, Shin Takasawa, Takashi Kitahara, Ryogo Shobatake. Resveratrol induced REG III and inhibited head and neck cancer progression [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 4199.