@Article{096504018X15201099883047,
AUTHOR = {Xiaohui Shen, Xia Gao, Hui Li, Yajun Gu, Junguo Wang},
TITLE = {TIMP-3 Increases the Chemosensitivity of Laryngeal Carcinoma to Cisplatin  via Facilitating Mitochondria-Dependent Apoptosis},
JOURNAL = {Oncology Research},
VOLUME = {27},
YEAR = {2019},
NUMBER = {1},
PAGES = {73--80},
URL = {http://www.techscience.com/or/v27n1/48662},
ISSN = {1555-3906},
ABSTRACT = {Laryngeal carcinoma is a type of head and neck carcinoma with a high incidence and mortality. Chemotherapy 
treatments of human laryngeal carcinoma may fail due to the development of chemoresistance. Tissue inhibitor 
of metalloproteinase 3 (TIMP-3) has been shown to be implicated in a number of pathological processes typical 
for cancer. The present study aims to investigate the involvement of TIMP-3 in the chemoresistance of laryngeal 
carcinoma. We showed that TIMP-3 expression was significantly decreased in chemoresistant laryngeal carcinoma tissues compared with chemosensitivity tissues. Patients with low TIMP-3 expression exhibited poorer 
overall survival than those with high TIMP-3 expression. Moreover, cisplatin-resistant Hep-2 cells (Hep-2/R) 
were associated with the inhibition of mitochondrial membrane potential (MtMP) depolarization after cisplatin 
challenge. In addition, cisplatin resulted in a more pronounced mitochondrial cytochrome c release into the 
cytoplasm in Hep-2 cells than in their resistant variants. Overexpression of TIMP-3 by an adenovirus encoding 
TIMP-3 cDNA remarkably enhanced cisplatin-induced apoptosis, cytochrome c release, and caspase activation 
in Hep-2/R cells, thereby sensitizing cancer cells to cisplatin. On the other hand, downregulation of TIMP-3 
markedly inhibited cisplatin-induced apoptosis in Hep-2 cells through attenuating mitochondria-dependent 
pathway activation. Taken together, these results demonstrate that decreased TIMP-3 expression may contribute to cisplatin resistance via inhibition of mitochondria-dependent apoptosis, indicating that forced TIMP-3 
expression may be a useful strategy to improve the efficacy of cisplatin to treat laryngeal carcinoma.},
DOI = {10.3727/096504018X15201099883047}
}