Is the resistance of gemcitabine for pancreatic cancer settled only by overexpression of deoxycytidine kinase?

被引：29

作者：

Funamizu, Naotake ^{[1
,2
]}

Okamoto, Aikou ^{[4
]}

Kamata, Yuko ^{[3
]}

Misawa, Takeyuki ^{[1
]}

Uwagawa, Tadashi ^{[1
]}

Gocho, Takeshi ^{[1
]}

Yanaga, Katsuhiko ^{[1
]}

Manome, Yoshinobu ^{[2
]}

机构：

[1] Jikei Univ, Sch Med, Dept Surg, Minato Ku, Tokyo 1058461, Japan

[2] Jikei Univ, Sch Med, Dept Mol Cell Biol, Minato Ku, Tokyo 1058461, Japan

[3] Jikei Univ, Sch Med, Inst DNA Med, Minato Ku, Tokyo 1058461, Japan

[4] Jikei Univ, Sch Med, Dept Gynecol, Minato Ku, Tokyo 1058461, Japan

来源：

ONCOLOGY REPORTS | 2010年 / 23卷 / 02期

关键词：

gemcitabine; pancreatic cancer; deoxycytidine kinase; deoxycytidine deaminase; tetra-hydro uridine; EQUILIBRATIVE NUCLEOSIDE TRANSPORTER-1; CELL LUNG-CANCER; IN-VIVO; CYTOSINE-ARABINOSIDE; INCREASED EXPRESSION; CYTIDINE DEAMINASE; ANTITUMOR-ACTIVITY; GENE-THERAPY; ADENOCARCINOMA; SENSITIVITY;

D O I：

10.3892/or_00000657

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The prognosis of pancreatic cancer remains poor, and the standard first-line chemotherapy with gemcitabine (GEM) has a response rate of less than 20%. Since expression of deoxycytidine kinase (dCK) seems important for improvement of GEM sensitivity, overexpression of dCK was investigated using pancreatic cancer cell lines (Panc-1, MIAPaCa-2 and BxPC-3). dCK gene was introduced into the cell lines by retrovirus and changes in IC50 were examined. Sensitivity of two pancreatic cancer cell lines to GEM elevated dramatically in comparison with control cells, but change of sensitivity remained at 1.8 times in BxPC-3. Since addition of tetrahydro uridine (THU), an inhibitor of deoxycytidine deaminase (CDA), increased the sensitivity 54-fold, overexpression of CDA seems to be the mechanism for improvement of the sensitivity. In Conclusion, dCK is a key enzyme of GEM, but resistance of GEM is not improved in all pancreatic cancer cells by overexpression of dCK. Combination treatment based on expression of GEM metabolism-related gene may become an effective therapy in the future.

引用

页码：471 / 475

页数：5

共 32 条

[1] Determinants of sensitivity and resistance to gemcitabine: The roles of human equilibrative nucleoside transporter 1 and deoxycytidine kinase in non-small cell lung cancer [J].

Achiwa, H ;

Oguri, T ;

Sato, S ;

Maeda, H ;

Niimi, T ;

Ueda, R .

CANCER SCIENCE, 2004, 95 (09) :753-757

[2] Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma [J].

Bengala, C ;

Guarneri, V ;

Giovannetti, E ;

Lencioni, M ;

Fontana, E ;

Mey, V ;

Fontana, A ;

Boggi, U ;

Del Chiaro, M ;

Danesi, R ;

Ricci, S ;

Mosca, F ;

Del Tacca, M ;

Conte, PF .

BRITISH JOURNAL OF CANCER, 2005, 93 (01) :35-40

[3] In vivo induction of resistance to gemcitabine results in increased expression of ribonucleotide reductase subunit M1 as the major determinant [J].

Bergman, AM ;

Eijk, PP ;

van Haperen, VWTR ;

Smid, K ;

Veerman, G ;

Hubeek, I ;

van den Ijssel, P ;

Ylstra, B ;

Peters, GJ .

CANCER RESEARCH, 2005, 65 (20) :9510-9516

[4] Synergistic antitumor activity of ZD6474, an inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling, with gemcitabine and ionizing radiation against pancreatic cancer [J].

Bianco, Cataldo ;

Giovannetti, Elisa ;

Ciardiello, Fortunato ;

Mey, Valentina ;

Nannizzi, Sara ;

Tortora, Giampaolo ;

Troiani, Teresa ;

Pasqualetti, Francesco ;

Eckhardt, Gail ;

de Liguoro, Mario ;

Ricciardi, Simona ;

Del Tacca, Mario ;

Raben, David ;

Cionini, Luca ;

Danesi, Romano .

CLINICAL CANCER RESEARCH, 2006, 12 (23) :7099-7107

[5]

Blackstock AW, 2001, CLIN CANCER RES, V7, P3263

[6] Fluvastatin synergistically enhances the antiproliferative effect of gemcitabine in human pancreatic cancer MIAPaCa-2 cells [J].

Bocci, G ;

Fioravanti, A ;

Orlandi, P ;

Bernardini, N ;

Collecchi, P ;

Del Tacca, M ;

Danesi, R .

BRITISH JOURNAL OF CANCER, 2005, 93 (03) :319-330

[7] KINETIC-STUDIES ON 2',2'-DIFLUORODEOXYCYTIDINE (GEMCITABINE) WITH PURIFIED HUMAN DEOXYCYTIDINE KINASE AND CYTIDINE DEAMINASE [J].

BOUFFARD, DY ;

LALIBERTE, J ;

MOMPARLER, RL .

BIOCHEMICAL PHARMACOLOGY, 1993, 45 (09) :1857-1861

[8]

CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P159

[9] Nucleoside anticancer drugs: the role of nucleoside transporters in resistance to cancer chemotherapy [J].

Damaraju, VL ;

Damaraju, S ;

Young, JD ;

Baldwin, SA ;

Mackey, J ;

Sawyer, MB ;

Cass, CE .

ONCOGENE, 2003, 22 (47) :7524-7536

[10] RETRACTED: RNA interference targeting the M2 subunit of ribonucleotide reductase enhances pancreatic adenocarcinoma chemosensitivity to gemcitabine (Retracted article. See FEB, 2023) [J].

Duxbury, MS ;

Ito, H ;

Zinner, MJ ;

Ashley, SW ;

Whang, EE .

ONCOGENE, 2004, 23 (08) :1539-1548

← 1 2 3 4 →