Effect of TTLL6 expression on CDDP sensitivity of EC109/CDDP cells in hypoxia/acidosis microenvironment.
Effect of TTLL6 expression on CDDP sensitivity of EC109/CDDP cells in hypoxia/acidosis microenvironment.
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DOI：
10.7150/jca.47694
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发表时间：
2020
影响因子：
3.9
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Qiu Y;Wu C;Li J;Tang M;Zhang S;Jing T;Liao Y;Wang H
多药耐药是食管癌有效治疗的主要障碍。在缺氧、酸中毒的微环境中更易发生。TTLL6是微管蛋白酪氨酸连接酶家族成员之一。本研究在体内外研究TTLL6对顺铂(CDDP)耐药细胞对顺铂敏感性的调节作用。在缺氧/酸中毒条件下，TTLL6在EC109/CDDP细胞中的过表达显著降低了CDDP对CDDP的IC50，并增加了CDDP诱导的细胞凋亡，而TTLL6在EC109/CDDP细胞中的过表达则表现出相反的作用。进一步的研究表明，TTLL6在机制上与ERBB2、TOPOIIA呈负相关，与凋亡相关因子Caspase9呈正相关。此外，动物模型证实TTLL6负调控化疗后移植瘤的生长。在EC109/CDDP细胞中，TTLL6的交替表达也调节了ERBB2、TOPOIIA和Caspase 9的表达。结论：TTLL6具有逆转EC109/CDDP细胞耐药的作用，为临床逆转化疗耐药提供了一种潜在的治疗策略。
Multidrug resistance is a major obstacle to the effective treatment of esophageal carcinoma. It occurs more readily in hypoxia and acidosis microenvironment. TTLL6 is one of Tubulin tyrosine ligase-like family members. In this study, the effect of TTLL6 on the regulation of cisplatin (CDDP) sensitivity was evaluated in CDDP-resistant esophageal carcinoma (EC) cells both in vitro and in vivo. In hypoxia/acidosis condition, overexpression of TTLL6 in EC109/CDDP cells significantly lowered the IC50 of CDDP and increased the CDDP-induced apoptosis; while knockdown of TTLL6 expression in EC109/CDDP cells exhibited the opposite effects. Further study showed that, mechanistically, TTLL6 was inversely correlated with ERBB2 and TOPOIIA, and positively correlated with apoptosis-associated factor Caspase 9. Furthermore, animal model confirmed that TTLL6 negatively regulated the growth of xenograft tumor after chemotherapy. Alternated expression of TTLL6 also regulated the expression of ERBB2, TOPOIIA and Caspase 9 in EC109/CDDP cells in vivo. In conclusion, our results suggest that TTLL6 could reverse the drug resistant of EC109/CDDP cells, it might provide a potential treatment strategy for the clinical reversing the chemotherapy resistance.
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DOI：
10.1016/j.cub.2009.12.062
发表时间：
2010-03-09
期刊：
Current biology : CB
影响因子：
--
作者：
Suryavanshi S;Eddé B;Fox LA;Guerrero S;Hard R;Hennessey T;Kabi A;Malison D;Pennock D;Sale WS;Wloga D;Gaertig J
通讯作者：
Gaertig J
影响因子：
3.8
作者：
McClusky, LM
通讯作者：
McClusky, LM
影响因子：
16.2
作者：
Feng, Rui-Mei;Zong, Yi-Nan;Xu, Rui-Hua
通讯作者：
Xu, Rui-Hua
影响因子：
3.1
作者：
Lu, Ji;Zhou, Kun;Ma, Baojin
通讯作者：
Ma, Baojin
影响因子：
4.3
作者：
Kang, Xiaozheng;Chen, Keneng;Chen, Xiaoxin
通讯作者：
Chen, Xiaoxin