Growth Suppression of Human Colorectal Cancer Cells with Mutated KRAS by 3-Deaza-cytarabine in 3D Floating Culture

被引：5

作者：

Luo, Hao ^{[1
]}

Nishi, Kensuke ^{[1
,2
]}

Ishikura, Shuhei ^{[1
,3
]}

Swain, Anthony ^{[1
]}

Morishige, Naoyuki ^{[1
,4
]}

Yazaki, Ryo ^{[5
]}

Ohshima, Takashi ^{[5
]}

Shirasawa, Senji ^{[1
,3
]}

Tsunoda, Toshiyuki ^{[1
,3
]}

机构：

[1] Fukuoka Univ, Dept Cell Biol, Fac Med, Fukuoka, Fukuoka, Japan

[2] Fukuoka Univ, Dept Otorhinolaryngol, Fac Med, Fukuoka, Fukuoka, Japan

[3] Fukuoka Univ, Cent Res Inst Adv Mol Med, Fukuoka, Fukuoka, Japan

[4] Ohshima Eye Hosp, Fukuoka, Fukuoka, Japan

[5] Kyushu Univ, Grad Sch Pharmaceut Sci, Fukuoka, Fukuoka, Japan

来源：

ANTICANCER RESEARCH | 2018年 / 38卷 / 07期

关键词：

Colorectal cancer; KRAS; 3D floating culture; nucleoside analogue; 5-bromouridine (BrUrd); 4-Amino-1-(beta-D-arabinofuranosyl)-2(1H)-pyridinone(3-deaza cytarabine); ACTIVATED KI-RAS; IN-VIVO; CRYPT MODEL; EXPRESSION; LINES; GEMCITABINE; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; PROLIFERATION; NUCLEOSIDE; MUTATIONS;

D O I：

10.21873/anticanres.12721

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background/Aim: During screening for compounds that selectively suppress growth of human colorectal cancer (CRC) spheroids with mutant (mt) KRAS, the uridine analogue, 5-bromouridine (BrUrd) was identified and its derivatives were explored. Materials and Methods: DNA incorporation in two-dimensional (2D) and three-dimensional floating (3DF) cultures was examined with the uridine analogue, 5-ethynyl-2'-deoxyuridine (EdU). The area of HKe3 CRC spheroids expressing wild type (wt) KRAS (HKe3-wtKRAS) and mtKRAS (HKe3-mtKRAS) were measured in 3DF culture with 11 BrUrd derivatives. Results: EdU was strongly incorporated into newly-synthesized DNA from HKe3-mtKRAS cells compared to HKe3-wtKRAS in 2D and 3DF culture. 3-Deaza-cytarabine, which has properties of BrUrd and cytidine, was the most effective inhibitor of HKe3-mtKRAS spheroids with the least toxicity to HKe3-wtKRAS. Growth suppression of 3-deazacytarabine was stronger than cytarabine in 2D culture, and toxicity was lower than gemcitabine in long-term 3DF culture. Conclusion: 3-Deaza-cytarabine exhibits properties useful for the treatment of CRC patients with mtKRAS.

引用

页码：4247 / 4256

页数：10

共 27 条

[1] A PHASE-I CLINICAL, PLASMA, AND CELLULAR PHARMACOLOGY STUDY OF GEMCITABINE [J].

ABBRUZZESE, JL ;

GRUNEWALD, R ;

WEEKS, EA ;

GRAVEL, D ;

ADAMS, T ;

NOWAK, B ;

MINEISHI, S ;

TARASSOFF, P ;

SATTERLEE, W ;

RABER, MN ;

PLUNKETT, W .

JOURNAL OF CLINICAL ONCOLOGY, 1991, 9 (03) :491-498

[2] Pancreatic Cancer Chemoresistance to Gemcitabine [J].

Amrutkar, Manoj ;

Gladhaug, Ivar P. .

CANCERS, 2017, 9 (11)

[3]

Baba I, 2000, CANCER RES, V60, P6886

[4] A PROPOSED MECHANISM OF ACTION OF 1-BETA-D-ARABINOFURANOSYL-CYTOSINE AS AN INHIBITOR OF GROWTH OF LEUKEMIC CELLS [J].

CHU, MY ;

FISCHER, GA .

BIOCHEMICAL PHARMACOLOGY, 1962, 11 (JUN) :423-+

[5] Nucleoside analogues and nucleobases in cancer treatment [J].

Galmarini, CM ;

Mackey, JR ;

Dumontet, C .

LANCET ONCOLOGY, 2002, 3 (07) :415-424

[6]

HEINEMANN V, 1988, CANCER RES, V48, P4024

[7]

HERTEL LW, 1990, CANCER RES, V50, P4417

[8]

JENSEN PO, 1993, CYTOMETRY, V14, P455

[9] Advances in the development of nucleoside and nucleotide analogues for cancer and viral diseases [J].

Jordheim, Lars Petter ;

Durantel, David ;

Zoulim, Fabien ;

Dumontet, Charles .

NATURE REVIEWS DRUG DISCOVERY, 2013, 12 (06) :447-464

[10] K-ras mutations and benefit from cetuximab in advanced colorectal cancer [J].

Karapetis, Christos S. ;

Khambata-Ford, Shirin ;

Jonker, Derek J. ;

O'Callaghan, Chris J. ;

Tu, Dongsheng ;

Tebbutt, Niall C. ;

Simes, R. John ;

Chalchal, Haji ;

Shapiro, Jeremy D. ;

Robitaille, Sonia ;

Price, Timothy J. ;

Shepherd, Lois ;

Au, Heather-Jane ;

Langer, Christiane ;

Moore, Malcolm J. ;

Zalcberg, John R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (17) :1757-1765

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