title: Enhanced anticancer activity of a protein phosphatase 2A inhibitor on chemotherapy and radiation in head and neck squamous cell carcinoma.
abstract: The aim of this study is to eliminate more cancer cells by promoting them from quiescence into cell cycle or by changing their molecular events, leading them to be sensitive to radiation or chemotherapy. Protein phosphatase 2A plays an important role in many cellular functions and regulates various biological processes. It is unclear that LB1, which is an inhibitor of protein phosphatase 2A, has enhanced anticancer activity on chemotherapy (cisplatin and 5-fluorourcil) and radiation in head and neck squamous cell carcinoma (HNSCC). Herein, we performed both in vitro and in vivo studies to determine the anticancer activity of LB1 on chemotherapy and radiation in HNSCC, with detection of p53 expression, AKT and MDM2 phosphorylation. In vitro studies indicated that, LB1 could significantly enhance the cytotoxicity of cisplatin, 5-fluorourcil, and radiation; LB1 could also significantly enhance the treatment effect of cisplatin in nude mice. The anticancer activity of LB1 was mediated by increased AKT phosphorylation and decreased p53 expression with increased MDM2 phosphorylation, especially when combined with cisplatin. Our data suggest a strategy of improving treatment effect through the enhanced anticancer activity of LB1 on cisplatin-based chemotherapy and radiation in HNSCC.
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Dong-wang
authors.initials: DW
authors.lastname: Zhu
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yong-xiang
authors.initials: YX
authors.lastname: Yuan
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jin-ke
authors.initials: JK
authors.lastname: Qiao
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Li-zhen
authors.initials: LZ
authors.lastname: Wang
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhi-yuan
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Department of Oral & Maxillofacial-Head & Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: zhonglp@hotmail.com.
authors.forename: Lai-ping
authors.initials: LP
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015153:Blotting, Western; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010879:Piperazines / Q000494:pharmacology*; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: C000595661:3-(4-methylpiperazine-1-carbonyl)-7-oxabicyclo(2.2.1)heptane-2-carboxylic acid; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D010879:Piperazines; D054648:Protein Phosphatase 2; D002945:Cisplatin; D005472:Fluorouracil
keywords: Chemotherapy; Head and neck squamous cell carcinoma; Protein phosphatase 2A inhibitor; Radiation