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PP-18


               Targeting MAST1 with shikonin overcomes cisplatin resistance in HNSCC


                                                               ,3
                             1
               Wen-Wen Li,  Ming-Jyh Sheu,  Pei-Yu Chou*
                                              1,2

               1  Department of Pharmacy, China Medical University Beigang Hospital, Yulin 651012,
                 Taiwan
               2  School of Pharmacy, College of Pharmacy, China Medical University, Taichung 406040,
                 Taiwan
               3  Department of Nursing, National Chi Nan University, Nantou 545301, Taiwan
               * E-mail: pychou@ncnu.edu.tw

               Abstract
                  Recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) demonstrate
               a poor prognosis. However, clinically, platinum-based chemotherapy still plays a central role in
               treating HNSCC. Nonetheless, resistance to platinum-based chemotherapy restricts its use to
               treat cancer patients.    A recent study indicated that microtubule-associated serine/threonine
               kinase 1 (MAST1) regulates CIS resistance. In the present study, shikonin was examined for its
               effects on the resistance to cisplatin. MAST1 protein expression and stages of HNSCC (human
               hypopharyngeal sample) showed a significant correlation from tissue array preparation. Our
               results demonstrated that shikonin effectively suppressed the MAST1 protein expression, which
               plays a role in cisplatin resistance. Also, shikonin exhibited the intrinsic and extrinsic apoptotic
               pathways that regulate the FaDu cell apoptosis signaling pathway. This study revealed that the
               synergistic administration of shikonin and cisplatin significantly suppresses the expression of
               MAST1. These findings suggest that including shikonin in combination therapy may offer a
               promising strategy to overcome cisplatin resistance in antitumor treatments.

               Keywords: MAST1; Shikonin; Cisplatin
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