机构:[1]Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, Los Angeles, CA 90095 USA[2]Capital Univ Med Sci, Affiliated Beijing Tongren Hosp, Dept Otolaryngol Head & Neck Surg, Beijing, Peoples R China临床科室耳鼻咽喉-头颈外科首都医科大学附属北京同仁医院首都医科大学附属同仁医院
Proteasome inhibitor PS-341 (also known as bortezomib) and histone deacetylase (HDAC) inhibitors have emerged as novel therapeutic agents for a variety of malignancies. In this study, we examined whether PS-341 and the HDAC inhibitor trichostatin A (TSA) induced apoptosis in head and neck squamous cell carcinoma (HNSCC), a common and lethal malignancy. We found that, although TSA treatment alone did not induce apoptosis in HNSCC cells, it significantly enhanced PS-341-induced apoptosis in HNSCC cells in vitro. Consistently, TSA significantly improved PS-341-mediated inhibition of HNSCC tumor growth in nude mice. Mechanistically, we found that TSA increased PS-341-induced Noxa expression and caspase activation in HNSCC cells. The knockdown of Noxa significantly reduced apoptosis induced by cotreatment of PS-341 and TSA. Taken together, our results provide new insight into the mechanisms of synergistic antitumor activity of the PS-341 and HDAC inhibitor regimen, offering a new therapeutic strategy for HNSCC patients. Mol Cancer Ther; 9(7); 1977-84. (C) 2010 AACR.
基金:
National Institute of Dental and Craniofacial ResearchUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [DE13848, DE15964]; NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [R01DE015964, R37DE013848] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [R01DE013848] Funding Source: NIH RePORTER
第一作者机构:[1]Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, Los Angeles, CA 90095 USA
通讯作者:
通讯机构:[1]Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, Los Angeles, CA 90095 USA[*1]Univ Calif Los Angeles, Sch Dent, Div Oral Biol & Med, CHS 33-030,Le Conte Ave, Los Angeles, CA 90095 USA
推荐引用方式(GB/T 7714):
Kim JinKoo,Guan Jean,Chang Insoon,et al.PS-341 and Histone Deacetylase Inhibitor Synergistically Induce Apoptosis in Head and Neck Squamous Cell Carcinoma Cells[J].MOLECULAR CANCER THERAPEUTICS.2010,9(7):1977-1984.doi:10.1158/1535-7163.MCT-10-0141.
APA:
Kim, JinKoo,Guan, Jean,Chang, Insoon,Chen, Xiaohong,Han, Demin&Wang, Cun-Yu.(2010).PS-341 and Histone Deacetylase Inhibitor Synergistically Induce Apoptosis in Head and Neck Squamous Cell Carcinoma Cells.MOLECULAR CANCER THERAPEUTICS,9,(7)
MLA:
Kim, JinKoo,et al."PS-341 and Histone Deacetylase Inhibitor Synergistically Induce Apoptosis in Head and Neck Squamous Cell Carcinoma Cells".MOLECULAR CANCER THERAPEUTICS 9..7(2010):1977-1984