Peimine可抑制前列腺癌细胞的生长和运动，并通过通过Ca2 + / CaMKII / JNK途径破坏细胞内钙稳态来诱导凋亡。,Journal of Cellular Biochemistry

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Peimine可抑制前列腺癌细胞的生长和运动，并通过通过Ca2 + / CaMKII / JNK途径破坏细胞内钙稳态来诱导凋亡。
Journal of Cellular Biochemistry ( IF 3.0 ) Pub Date : 2019-05-12 , DOI: 10.1002/jcb.28870
Hailin Tan ₁ , Guiming Zhang ₁ , Xuecheng Yang ₁ , Tao Jing ₁ , Daqing Shen ₂ , Xinsheng Wang ₁

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前列腺癌（PC）是人类最常见的恶性肿瘤之一。Peimine（PM）是一种贝母中的生物活性物质。先前的研究表明，PM可以抑制多种癌症的发生。但是，尚未阐明PM在PC中的作用及其相关机制。钙（Ca2 +）是参与多种细胞过程的重要细胞内信使。在这项研究中，我们发现适当剂量的PM（2.5、5和10μM）会显着抑制PC细胞（DU-145，LNCap和PC-3）的生长，但对正常前列腺细胞没有显着影响（RWPE-1）。此外，PM处理可抑制PC-3细胞的侵袭和迁移，并阻断上皮-间质转化过程。这些作用表现出剂量依赖性。此外，目前的结果还表明，PM处理显着增加了Ca2 +的浓度，增加的Ca2 +促进了Ca2 + /钙调蛋白依赖性蛋白激酶II（CaMKII）和c-Jun N-末端激酶（JNK）的磷酸化，进一步抑制了其生长和侵袭PC-3细胞的凋亡，并诱导其凋亡。Ca2 +螯合剂BAPTA-AM（1μM）可以抵消细胞内Ca2 +浓度的增加。同样，JNK途径抑制剂SP600125（10μM）也抑制细胞生长和侵袭并诱导细胞凋亡。另外，在裸鼠中的实验表明，PM通过Ca2 + / CaMKII / JNK信号通路抑制了肿瘤形成。总之，我们的结果表明，PM通过Ca2 + / CaMKII / JNK途径破坏细胞内钙稳态，从而抑制了前列腺癌细胞的生长和运动并诱导了细胞凋亡。

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Peimine inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca2+ /CaMKII/JNK pathway.

Prostate cancer (PC) is one of the most common malignant tumors in man. Peimine (PM) is a bioactive substance isolated from Fritillaria. Previous studies have shown that PM could inhibit the occurrence of a variety of cancers. However, the roles of PM in PC and its related mechanism have not been elucidated. Calcium (Ca2+ ) is an important intracellular messenger involved in a variety of cell processes. In this study, we found that the appropriate doses of PM (2.5, 5, and 10 μM) significantly inhibited the growth of PC cells (DU-145, LNCap, and PC-3), but has no significant effect on normal prostate cells (RWPE-1). In addition, PM treatment inhibited the invasion and migration of PC-3 cells and blocked the epithelial-mesenchymal transition process. These effects were exhibited a dose-dependent manner. Furthermore, the current results also showed that PM treatment significantly increased the Ca2+ concentration, the increased Ca2+ promoted the phosphorylation of Ca2+ /calmodulin-dependent protein kinase II (CaMKII) and c-Jun N-terminal kinase (JNK), further inhibited the growth and invasion of PC-3 cells, and induced its apoptosis. Ca2+ chelator BAPTA-AM (1 μM) could counteract the increase of intracellular Ca2+ concentration. Similarly, JNK pathway inhibitor SP600125 (10 μM) also inhibited cell growth and invasion and induced apoptosis. In addition, experiments in nude mice showed that PM inhibited tumor formation through Ca2+ /CaMKII/JNK signaling pathway. In conclusion, our results show that PM inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca2+ /CaMKII/JNK pathway.

更新日期：2019-11-01

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