Lactate Dehydrogenase B Is Associated with the Response to Neoadjuvant Chemotherapy in Oral Squamous Cell Carcinoma

doi:10.1371/journal.pone.0125976

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第一研究室

	Lactate Dehydrogenase B Is Associated with the Response to Neoadjuvant Chemotherapy in Oral Squamous Cell Carcinoma
	Sun, Wenyi 1; Zhang, Xiaomin 2; Ding, Xu 2; Li, Huaiqi 2; Geng, Meiyu1 ; Xie, Zuoquan1 ; Wu, Heming 2; Huang, Min1
刊名	PLOS ONE
	2015-05-14
卷号	10 期号:5
ISSN号	1932-6203
DOI	10.1371/journal.pone.0125976
文献子类	Article
英文摘要	Oral squamous cell carcinoma (OSCC) comprises a subset of head and neck squamous cell carcinoma (HNSCC) with poor therapeutic outcomes and high glycolytic dependency. Neoadjuvant chemotherapy regimens of docetaxel, cisplatin and 5-fluorouracil (TPF) are currently accepted as standard regimens for HNSCC patients with a high risk of distant metastatic spread. However, the antitumor outcomes of TPF neoadjuvant chemotherapy in HNSCC remain controversial. This study investigated the role of lactate dehydrogenase B (LDHB), a key glycolytic enzyme catalyzing the inter-conversion between pyruvate and lactate, in determining chemotherapy response and prognosis in OSCC patients. We discovered that a high protein level of LDHB in OSCC patients was associated with a poor response to TPF regimen chemotherapy as well as poor overall survival and disease-free survival. Our in-depth study revealed that high LDHB expression conferred resistance to taxol but not 5-fluorouracil or cisplatin. LDHB deletion sensitized OSCC cell lines to taxol, whereas the introduction of LDHB decreased sensitivity to taxol treatment. Taxol induced a pronounced impact on LDHB-downregulated OSCC cells in terms of apoptosis, G2/Mphase cell cycle arrest and energy metabolism. In conclusion, our study highlighted the critical role of LDHB in OSCC and proposed that LDHB could be used as a biomarker for the stratification of patients for TPF neoadjuvant chemotherapy and the determination of prognosis in OSCC patients.
资助项目	National Natural Science Foundation of China[81222049] ; National Natural Science Foundation of China[81202549] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2012ZX09301001-004] ; National Science and Technology Major Project of the Ministry of Science and Technology of China[2012ZX09301001-007] ; Pujiang Scholar Program Grant by the Shanghai Metropolitan Government[12PJ1410400]
WOS关键词	INDUCIBLE FACTOR-I ; CANCER-CELLS ; NECK-CANCER ; INDUCTION CHEMOTHERAPY ; BREAST-CANCER ; TYROSINE PHOSPHORYLATION ; POOR-PROGNOSIS ; PHASE-III ; HEAD ; TAXOL
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000354545600034
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276529]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Xie, Zuoquan
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 200031, Peoples R China; 2.Nanjing Med Univ, Affiliated Hosp Stomatol, Dept Oral & Maxillofacial Surg, Jiangsu Key Lab Oral Dis, Nanjing, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Sun, Wenyi,Zhang, Xiaomin,Ding, Xu,et al. Lactate Dehydrogenase B Is Associated with the Response to Neoadjuvant Chemotherapy in Oral Squamous Cell Carcinoma[J]. PLOS ONE,2015,10(5).
APA	Sun, Wenyi.,Zhang, Xiaomin.,Ding, Xu.,Li, Huaiqi.,Geng, Meiyu.,...&Huang, Min.(2015).Lactate Dehydrogenase B Is Associated with the Response to Neoadjuvant Chemotherapy in Oral Squamous Cell Carcinoma.PLOS ONE,10(5).
MLA	Sun, Wenyi,et al."Lactate Dehydrogenase B Is Associated with the Response to Neoadjuvant Chemotherapy in Oral Squamous Cell Carcinoma".PLOS ONE 10.5(2015).