Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation.
Enhancement by Nano-Diamino-Tetrac of Antiproliferative Action of Gefitinib on Colorectal Cancer Cells: Mediation by EGFR Sialylation and PI3K Activation.
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DOI：
10.1007/s12672-018-0341-x
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发表时间：
2018-12
影响因子：
3
通讯作者：
Davis PJ
中科院分区：
文献类型：
--
作者：
Chang TC;Chin YT;Nana AW;Wang SH;Liao YM;Chen YR;Shih YJ;Changou CA;Yang YS;Wang K;Whang-Peng J;Wang LS;Stain SC;Shih A;Lin HY;Wu CH;Davis PJ
耐药性使吉非替尼的临床使用变得复杂。四碘甲状腺乙酸（tetrac）和纳米二氨基四乙酸（NDAT）已在体外和异种移植物中显示具有抗增殖/血管生成特性，并增强其他抗癌药物的抗增殖活性。在本研究中，我们研究了NDAT对吉非替尼在人结直肠癌细胞中的抗癌活性的影响。β-半乳糖苷α-2，6-唾液酸转移酶1（ST 6 Gal 1）催化与结直肠癌吉非替尼耐药相关的EGFR唾液酸化，也对此进行了研究。吉非替尼抑制HT-29细胞（K-ras野生型）的细胞增殖，NDAT显著增强吉非替尼的抗增殖作用。吉非替尼仅在高浓度下抑制HCT 116细胞（K-ras突变体）的细胞增殖，NDAT进一步增强了这种抑制作用。NDAT通过抑制ST 6 Gal 1活性和PI 3 K活化增强吉非替尼诱导的吉非替尼耐药结直肠癌细胞的抗增殖作用此外，NDAT增强吉非替尼诱导的结直肠癌HCT 116细胞异种移植荷瘤裸鼠的抗癌活性。结果表明，NDAT可能与吉非替尼作为结直肠癌联合治疗的应用。
Drug resistance complicates the clinical use of gefitinib. Tetraiodothyroacetic acid (tetrac) and nano-diamino-tetrac (NDAT) have been shown in vitro and in xenografts to have antiproliferative/angiogenic properties and to potentiate antiproliferative activity of other anticancer agents. In the current study, we investigated the effects of NDAT on the anticancer activities of gefitinib in human colorectal cancer cells. β-Galactoside α-2,6-sialyltransferase 1 (ST6Gal1) catalyzes EGFR sialylation that is associated with gefitinib resistance in colorectal cancers, and this was also investigated. Gefitinib inhibited cell proliferation of HT-29 cells (K-ras wild-type), and NDAT significantly enhanced the antiproliferative action of gefitinib. Gefitinib inhibited cell proliferation of HCT116 cells (K-ras mutant) only in high concentration, and this was further enhanced by NDAT. NDAT enhancedd gefitinib-induced antiproliferation in gefitinib-resistant colorectal cancer cells by inhibiting ST6Gal1 activity and PI3K activation. Furthermore, NDAT enhanced gefitinib-induced anticancer activity additively in colorectal cancer HCT116 cell xenograft-bearing nude mice. Results suggest that NDAT may have an application with gefitinib as combination colorectal cancer therapy.
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影响因子：
37.3
作者：
Hu T;Li C
通讯作者：
Li C
影响因子：
--
作者：
Baba Y;Fujii M;Tokumaru Y;Kato Y
通讯作者：
Kato Y
DOI：
10.1042/bj20110112
发表时间：
2011-07-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Barbolina MV;Burkhalter RJ;Stack MS
通讯作者：
Stack MS
影响因子：
11.5
作者：
Ono, Mayumi;Kuwano, Michihiko
通讯作者：
Kuwano, Michihiko
影响因子：
3.1
作者：
Shitoh, K;Koinuma, K;Nagai, H
通讯作者：
Nagai, H