MCT4 as a potential therapeutic target for metastatic gastric cancer with peritoneal carcinomatosis.
MCT4 as a potential therapeutic target for metastatic gastric cancer with peritoneal carcinomatosis.
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DOI：
10.18632/oncotarget.9523
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发表时间：
2016-07-12
期刊：
影响因子：
--
通讯作者：
Kang WK
中科院分区：
文献类型：
--
作者：
Lee JY;Lee I;Chang WJ;Ahn SM;Lim SH;Kim HS;Yoo KH;Jung KS;Song HN;Cho JH;Kim SY;Kim KM;Lee S;Kim ST;Park SH;Lee J;Park JO;Park YS;Lim HY;Kang WK
单羧酸转运蛋白（MCT）在糖酵解和适应酸中毒的上调中发挥重要作用。然而，MCT在胃癌（GC）中的作用尚未完全了解。我们研究了一种新的癌症治疗GC的潜在利用。我们通过使用靶向MCT的siRNA进行体外和体内试验，表征了MCT亚型1、2和4的表达模式，并研究了MCT在GC中的作用。在胃癌细胞系中，MCT 1、2和4表达上调，表达水平不同;与MCT 2相比，MCT 1和MCT 4在胃癌细胞系中表达更广泛。通过siRNA或AR-C155858抑制MCT降低GC细胞系中的细胞活力和乳酸摄取。在异种移植模型中也证实了MCT对肿瘤生长的抑制作用。此外，GC细胞中的MCT抑制增加了细胞对放疗或化疗的敏感性。与正常胃组织相比，肿瘤中MCT 1和MCT 2的表达水平没有显著变化，而MCT 4的表达显著增加。最重要的是，MCT 4在腹水的恶性细胞中高度过表达，并且其沉默导致恶性腹水中肿瘤细胞增殖和乳酸摄取减少。我们的研究表明，MCT 4是胃癌伴腹膜癌转移的临床相关靶点。
Monocarboxylate transporters (MCTs) play a major role in up-regulation of glycolysis and adaptation to acidosis. However, the role of MCTs in gastric cancer (GC) is not fully understood. We investigated the potential utilization of a new cancer therapy for GC. We characterized the expression patterns of the MCT isoforms 1, 2, and 4 and investigated the role of MCT in GC through in vitro and in vivo tests using siRNA targeting MCTs. In GC cell lines, MCT1, 2, and 4 were up-regulated with different expression levels; MCT1 and MCT4 were more widely expressed in GC cell lines compared with MCT2. Inhibition of MCTs by siRNA or AR-C155858 reduced cell viability and lactate uptake in GC cell lines. The effect of inhibition of MCTs on tumor growth was also confirmed in xenograft models. Furthermore, MCT inhibition in GC cells increased the sensitivity of cells to radiotherapy or chemotherapy. Compared with normal gastric tissue, no significant alterations of expression levels in tumors were identified for MCT1 and MCT2, whereas a significant increase in MCT4 expression was observed. Most importantly, MCT4 was highly overexpressed in malignant cells of acsites and its silencing resulted in reduced tumor cell proliferation and lactate uptake in malignant ascites. Our study suggests that MCT4 is a clinically relevant target in GC with peritoneal carcinomatosis.
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影响因子：
3.5
作者：
Asada, K;Miyamoto, K;Ushijima, T
通讯作者：
Ushijima, T
影响因子：
4.1
作者：
Dimmer, KS;Friedrich, B;Bröer, S
通讯作者：
Bröer, S
DOI：
10.1016/0960-7404(92)90034-i
发表时间：
1992-10-01
期刊：
Surgical oncology
影响因子：
--
作者：
Moriguchi, S;Maehara, Y;Nose, Y
通讯作者：
Nose, Y
影响因子：
9.7
作者：
Amorim, Ricardo;Pinheiro, Celine;Baltazar, Fatima
通讯作者：
Baltazar, Fatima
影响因子：
45.3
作者：
Lee, Jeeyun;Lim, Do Hoon;Kang, Won Ki
通讯作者：
Kang, Won Ki