Inhibition of cancer cell proliferation by midazolam by targeting transient receptor potential melastatin 7.
Inhibition of cancer cell proliferation by midazolam by targeting transient receptor potential melastatin 7.
复制标题
咪达唑仑通过靶向瞬时受体电位 melastatin 7 抑制癌细胞增殖
DOI：
10.3892/ol.2013.1129
复制
发表时间：
2013-03
期刊：
影响因子：
2.9
通讯作者：
Yan G
中科院分区：
文献类型：
--
作者：
Dou Y;Li Y;Chen J;Wu S;Xiao X;Xie S;Tang L;Yan M;Wang Y;Lin J;Zhu W;Yan G
瞬时受体电位melastatin 7（TRPM 7）是一种钙离子通道，存在于肿瘤细胞中，参与肿瘤细胞的生长和增殖。本研究使用苯二氮类麻醉剂咪达唑仑，间接干预TRPM 7的表达，抑制癌细胞增殖。咪达唑仑能显著抑制FaDu人下咽鳞癌细胞的生长和增殖，并诱导细胞周期阻滞于G 0/G1期，阻断Rb的激活。中枢型和外周型苯二氮卓类受体拮抗剂没有废除增殖抑制咪达唑仑，而特异性TRPM 7激动剂缓激肽逆转这种作用。此外，其他苯二氮卓类药物，地西泮和氯硝西泮也表现出抗增殖活性。对癌细胞生长和增殖的抑制活性，结合TRPM依赖性机制，揭示了咪达唑仑作为TRPM 7抑制剂的抗癌潜力，并支持TRPM 7是药物干预的有价值靶点的建议。
Transient receptor potential melastatin 7 (TRPM7), a Ca2+-permeable channel, has been demonstrated to be present in cancer cells and involved in their growth and proliferation. The present study used midazolam, a benzodiazepine class anesthesic, to pharmacologically intervene in the expression of TRPM7 and to inhibit cancer cell proliferation. Midazolam significantly inhibited the growth and proliferation of FaDu human hypopharyngeal squamous cell carcinoma cells, concurring with the induction of G0/G1 cell cycle arrest and blockage of Rb activation. Central-type and peripheral-type benzodiazepine receptor antagonists did not abrogate proliferation inhibition by midazolam, while the specific TRPM7 agonist bradykinin reversed this effect. In addition, other benzodiazepines, diazepam and clonazepam also exhibited anti-proliferative activities. The inhibitory activity on cancer cell growth and proliferation, combined with the TRPM-dependent mechanism, reveals the anticancer potential of midazolam as a TRPM7 inhibitor and supports the suggestion that TRPM7 is a valuable target for pharmaceutical intervention.
登录
查看更多内容
影响因子：
3.6
作者：
Zhu, Wenbo;Ou, Yanqiu;Yan, Guangmei
通讯作者：
Yan, Guangmei
影响因子：
5.5
作者：
Guilbert, Arnaud;Gautier, Mathieu;Ouadid-Ahidouch, Halima
通讯作者：
Ouadid-Ahidouch, Halima
影响因子：
11.2
作者：
Jiang, Jie;Li, Ming-Hua;Xiong, Zhi-Gang
通讯作者：
Xiong, Zhi-Gang
影响因子：
8.8
作者：
Exadaktylos, Aristomenis K.;Buggy, Donal J.;Sessler, Daniel I.
通讯作者：
Sessler, Daniel I.
EGF 通过上调 TRPM7 增强癌细胞的迁移。
影响因子：
4
作者：
Gao, Haixia;Chen, Xingjuan;Zhang, Hailin
通讯作者：
Zhang, Hailin