Lovastatin inhibits human B lymphoma cell proliferation by reducing intracellular ROS and TRPC6 expression.
Lovastatin inhibits human B lymphoma cell proliferation by reducing intracellular ROS and TRPC6 expression.
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DOI：
10.1016/j.bbamcr.2014.02.002
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发表时间：
2014-05
影响因子：
5.1
通讯作者：
Shen, Bao-Zhong
中科院分区：
文献类型：
--
作者：
Song, Xiang;Liu, Bing-Chen;Lu, Xiao-Yu;Yang, Li-Li;Zhai, Yu-Jia;Eaton, Amity F.;Thai, Tiffany L.;Eaton, Douglas C.;Ma, He-Ping;Shen, Bao-Zhong
关键词：
临床证据表明，他汀类药物可降低癌症发病率和死亡率。然而，缺乏体外数据来说明他汀类药物降低癌细胞恶性程度的机制。我们以人B淋巴瘤Daudi细胞为模型，发现洛伐他汀抑制了对照Daudi细胞的增殖，而外源性胆固醇(CHO)则刺激了细胞周期的进展，但当瞬时受体电位规范6(TRPC6)通道被破坏时，洛伐他汀对细胞周期进程没有影响。洛伐他汀通过降低或增加p47-Phox和gp91-Phox(NOX2)的表达来降低细胞内的ROS水平，而CHO则通过增加或降低细胞内的ROS水平。用模拟的超氧化物歧化酶(Temol)或NADPH氧化酶抑制剂(Apocynin)降低细胞内ROS会抑制细胞的增殖，特别是在CHO处理的细胞中。通过用SKF-96365抑制TRPC6来模拟坦普尔或罗布麻素的作用。洛伐他汀通过CHO依赖机制降低TRPC6的表达和活性，而CHO通过ROS依赖机制增加TRPC6的表达和活性。与TRPC6是钙离子通透通道的事实一致，洛伐他汀降低，而CHO升高，细胞内钙离子也通过ROS途径。这些数据表明洛伐他汀通过减少细胞膜CHO、细胞内ROS、TRPC6的表达和活性以及细胞内钙离子来抑制恶性B细胞的增殖。
Clinical evidence suggests that statins reduce cancer incidence and mortality. However, there is lack of in vitro data to show the mechanism by which statins can reduce the malignancies of cancer cells. We used a human B lymphoma Daudi cells as a model and found that lovastatin inhibited, whereas exogenous cholesterol (Cho) stimulated, proliferation cell cycle progression in control Daudi cells, but not in the cells when transient receptor potential canonical 6 (TRPC6) channel was knocked down. Lovastatin decreased, whereas Cho increased, the levels of intracellular reactive oxygen species (ROS) respectively by decreasing or increasing the expression of p47-phox and gp91-phox (NOX2). Reducing intracellular ROS with either a mimetic superoxide dismutase (TEMPOL) or a NADPH oxidase inhibitor (apocynin) inhibited cell proliferation, particularly in Cho-treated cells. The effects of TEMPOL or apocynin were mimicked by inhibition of TRPC6 with SKF-96365. Lovastatin decreased TRPC6 expression and activity via a Cho-dependent mechanism, whereas Cho increased TRPC6 expression and activity via an ROS-dependent mechanism. Consistent with the fact that TRPC6 is a Ca2+-permeable channel, lovastatin decreased, but Cho increased, intracellular Ca2+ also via ROS. These data suggest that lovastatin inhibits malignant B cell proliferation by reducing membrane Cho, intracellular ROS, TRPC6 expression and activity, and intracellular Ca2+.
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影响因子：
3.7
作者：
Bansal D;Undela K;D'Cruz S;Schifano F
通讯作者：
Schifano F
影响因子：
37.8
作者：
Froehlich, Georg Marcus;Rufibach, Kaspar;Ruschitzka, Frank
通讯作者：
Ruschitzka, Frank
影响因子：
3.8
作者：
Guilbert A;Dhennin-Duthille I;Hiani YE;Haren N;Khorsi H;Sevestre H;Ahidouch A;Ouadid-Ahidouch H
通讯作者：
Ouadid-Ahidouch H
影响因子：
11.2
作者：
Jacobs, Eric J.;Newton, Christina C.;Gapstur, Susan M.
通讯作者：
Gapstur, Susan M.
洛伐他汀减弱环孢素 A 对培养的皮质集合管主细胞紧密连接和细胞凋亡的影响
DOI：
10.1152/ajprenal.00074.2013
发表时间：
2013-08-01
影响因子：
4.2
作者：
Liu, Bing-Chen;Song, Xiang;Ma, He-Ping
通讯作者：
Ma, He-Ping