Effect of 5-fluorouracil on G1 phase cell cycle regulation in oral cancer cell lines

被引:56
作者
Li, MH [1 ]
Ito, D [1 ]
Sanada, M [1 ]
Odani, T [1 ]
Hatori, M [1 ]
Iwase, M [1 ]
Nagumo, M [1 ]
机构
[1] Showa Univ, Sch Dent, Dept Oral & Maxillofacial Surg 2, Tokyo 1458515, Japan
关键词
5-FU; cyclin; cyclin-dependent kinases (CDKs); CDK inhibitors (CKIs);
D O I
10.1016/S1368-8375(03)00136-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
5-Fluorouracil (5-FU) has been widely used for chemotherapy of head and neck cancer, and is known to affect the cell cycle and induce apoptotic death of cancer cells. However, the molecular actions of 5-FU on the cell cycle regulatory mechanism have not been fully explained. Herein we analyzed the effects of 5-FU on the expression of G1/S-related cell cycle regulators in oral cancer cell tines. In vitro 5-FU treatment of oral cancer cells resulted in an increase in G1/S phase cells. p21 expression was augmented by 5-FU without any notable changes in p53 expression. A remarkable up-regulation of cyclin E and a concomitant down-regulation of cyclin D were observed after 24 h 5-FU treatment. Our results suggest that 5-FU-induced changes in cell cycle regulation of oral cancer cells might associate with an alteration of G1 cyclins expression. p21 was remarkably up-regulated, but it was speculated that its activity might be cancelled by an increased binding to CDK4. (C) 2003 Elsevier Ltd. All rights reserved.
引用
收藏
页码:63 / 70
页数:8
相关论文
共 29 条
[1]   CRYSTAL-STRUCTURE OF CYCLIN-DEPENDENT KINASE-2 [J].
DEBONDT, HL ;
ROSENBLATT, J ;
JANCARIK, J ;
JONES, HD ;
MORGAN, DO ;
KIM, SH .
NATURE, 1993, 363 (6430) :595-602
[2]   OVERVIEW OF COMBINED MODALITY THERAPIES FOR HEAD AND NECK-CANCER [J].
DIMERY, IW ;
HONG, WK .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (02) :95-111
[3]   DNA damage-induced G1 arrest in hematopoietic cells is overridden following phosphatidylinositol 3-kinase-dependent activation of cyclin-dependent kinase 2 [J].
Eapen, AK ;
Henry, MK ;
Quelle, DE ;
Quelle, FW .
MOLECULAR AND CELLULAR BIOLOGY, 2001, 21 (18) :6113-6121
[4]  
EIDELBERGER C, 1983, ADV ENZYMOL RELAT AR, V54, P58
[5]  
ELDEIRY WS, 1994, CANCER RES, V54, P1169
[6]   WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION [J].
ELDEIRY, WS ;
TOKINO, T ;
VELCULESCU, VE ;
LEVY, DB ;
PARSONS, R ;
TRENT, JM ;
LIN, D ;
MERCER, WE ;
KINZLER, KW ;
VOGELSTEIN, B .
CELL, 1993, 75 (04) :817-825
[7]   Induction of p18(INK4c) and its predominant association with CDK4 and CDK6 during myogenic differentiation [J].
Franklin, DS ;
Xiong, Y .
MOLECULAR BIOLOGY OF THE CELL, 1996, 7 (10) :1587-1599
[8]   PHARMACOKINETIC MODULATION OF PLASMA 5-FLUOROURACIL CONCENTRATIONS TO POTENTIATE THE ANTITUMOR-ACTIVITY OF CONTINUOUS VENOUS INFUSION OF 5-FLUOROURACIL [J].
FUJII, S ;
FUKUSHIMA, M ;
SHIMAMOTO, Y ;
SHIRASAKA, T .
JAPANESE JOURNAL OF CANCER RESEARCH, 1989, 80 (06) :509-512
[9]   EFFECTS OF THE PLASMA-CONCENTRATION OF 5-FLUOROURACIL AND THE DURATION OF CONTINUOUS VENOUS INFUSION OF 5-FLUOROURACIL WITH AN INHIBITOR OF 5-FLUOROURACIL DEGRADATION ON YOSHIDA SARCOMAS IN RATS [J].
FUJII, S ;
SHIMAMOTO, Y ;
OHSHIMO, H ;
IMAOKA, T ;
MOTOYAMA, M ;
FUKUSHIMA, M ;
SHIRASAKA, T .
JAPANESE JOURNAL OF CANCER RESEARCH, 1989, 80 (02) :167-172
[10]   Activation and repression of p21WAF1/CIP1 transcription by RB binding proteins [J].
Gartel, AL ;
Goufman, E ;
Tevosian, SG ;
Shih, H ;
Yee, AS ;
Tyner, AL .
ONCOGENE, 1998, 17 (26) :3463-3469