Valproic acid: Growth inhibition of head and neck cancer by induction of terminal differentiation and senescence

被引：35

作者：

Gan, Chai Phei ^{[1
,2
]}

Hamid, Sharifah ^{[1
]}

Hor, Seen Yii ^{[1
]}

Zain, Rosnah Binti ^{[2
]}

Ismail, Siti Mazlipah ^{[3
]}

Mustafa, Wan Mahadzir Wan ^{[4
]}

Teo, Soo Hwang ^{[1
]}

Saunders, Nicholas ^{[5
]}

Cheong, Sok Ching ^{[1
,3
]}

机构：

[1] Sime Darby Med Ctr, Outpatient Ctr, Canc Res Initiat Fdn, Oral Canc Res Team, Subang Jaya 47500, Selangor, Malaysia

[2] Univ Malaya, Oral Canc Res & Coordinating Ctr, Kuala Lumpur 50603, Malaysia

[3] Univ Malaya, Dept Oral & Maxillofacial Surg, Kuala Lumpur 50603, Malaysia

[4] Hosp Kuala Lumpur, Dept Oral & Maxillofacial Surg, Kuala Lumpur 50588, Malaysia

[5] Univ Queensland, Ctr Immunol & Canc Res, Brisbane, Qld 4072, Australia

来源：

HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK | 2012年 / 34卷 / 03期

关键词：

histone deacetylase inhibitor; valproic acid; head and neck cancer; terminal differentiation; senescence; HISTONE DEACETYLASE INHIBITORS; CELLS IN-VITRO; MAGNESIUM VALPROATE; EPIGENETIC THERAPY; SODIUM VALPROATE; CARCINOMA-CELLS; G2/M ARREST; EXPRESSION; APOPTOSIS; COMBINATION;

D O I：

10.1002/hed.21734

中图分类号：

R76 [耳鼻咽喉科学];

学科分类号：

100213 ;

摘要：

Background There are limited studies on the effects of drugs that modulate epigenetic regulation for head and neck squamous cell carcinoma (HNSCC). This study determined the effect of valproic acid (VPA) on HNSCC. Methods. Growth inhibition effects of VPA alone or in combination with 5-aza-2'deoxycytidine (5-aza-dC) or all-trans retinoic acid (ATRA) was evaluated with MTT and clonogenic assays on 5 HNSCC cell lines. The mechanism of growth inhibition was investigated by looking at markers of terminal differentiation and senescence. Results. Growth inhibition profiles of HNSCC cell lines varied in response to VPA. Inhibition of clonogenic survival in response to VPA was associated with an upregulation of p21, expression of terminal differentiation markers, and cellular senescence. Notably, a combination treatment of 5-Aza-dC-VPA-ATRA enhanced growth inhibition in cells resistant to VPA. Conclusion. VPA is a potent inhibitor of proliferation in some HNSCC cell lines, and may be used to treat HNSCC. (C) 2011 Wiley Periodicals, Inc. Head Neck 34: 344-353, 2012

引用

页码：344 / 353

页数：10

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