title: Inhibition of glucose transporter 1 (GLUT1) chemosensitized head and neck cancer cells to cisplatin.
abstract: Glucose transporter 1 (GLUT1) facilitates the cellular uptake of glucose and is overexpressed in most cancers. The altered expression of GLUT1 may influence the sensitivity of tumor cells to chemotherapy. This study investigated whether the knockdown of GLUT1 expression to sensitize head and neck cancer cells to the chemotherapy drug cisplatin in vitro. Anti-GLUT1 antibody was used to block activity of GLUT1 protein, and GLUT1-shRNA was used to knock down its mRNA expression in Cal27 cells. Immunocytochemistry, Western blot, and qRT-PCR were used to detect expression of GLUT1 mRNA and protein, respectively. Lentivirus was used to carrying GLUT1-shRNA to knockdown GLUT1 expression in Cal27 cells for MTT and flow cytometry analyses of cell viability and apoptosis, respectively. Glucose uptake assay was used to assess the changes in glucose levels in Cal27 cells. It showed that GLUT1 mRNA and protein were expressed in Cal27 cells, and GLUT1 protein was localized on the cell membrane. Both anti-GLUT1 antibody and GLUT1-shRNA sensitized Cal27 cells to cisplatin treatment under both normoxia and hypoxia conditions. Anti- GLUT1 antibody and GLUT1-shRNA inhibited tumor cell growth in vitro and induced them to undergo apoptosis. GLUT1-shRNA also suppressed tumor cell uptake of glucose into the cells. Our findings suggest that inhibition of GLUT1 activity and expression can sensitize Cal27 cells to cisplatin treatment in both normoxic and hypoxic conditions. These data could be further verified in animal xenografts before potential application as a clinical adjuvant or neoadjuvant therapy of head and neck cancer with cisplatin.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Stomatology Hospital, Tongji University, Shanghai, China. lshjlchm@163.com.
authors.forename: Yao-Dong
authors.initials: YD
authors.lastname: Wang
authors.forename: Sheng-Jiao
authors.initials: SJ
authors.lastname: Li
authors.forename: Jian-Xing
authors.initials: JX
authors.lastname: Liao
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D051272:Glucose Transporter Type 1; D034741:RNA, Small Interfering; C495677:SLC2A1 protein, human; D005947:Glucose; D002945:Cisplatin