Methylseleninic acid suppresses pancreatic cancer growth involving multiple pathways.
Methylseleninic acid suppresses pancreatic cancer growth involving multiple pathways.
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DOI：
10.1080/01635581.2014.868911
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Lü J
中科院分区：
文献类型：
--
作者：
Wang L;Hu H;Wang Z;Xiong H;Cheng Y;Liao JD;Deng Y;Lü J
甲基硒酸（MSeA）作为一种潜在的治疗胰腺癌的新药物，在细胞培养和异种移植模型中进行了评估。结果显示，MSeA在大多数人和小鼠胰腺癌细胞系中诱导G1细胞周期阻滞和凋亡，而在人PANC-1和PANC-28细胞系中诱导G2细胞周期阻滞。与我们之前在MSeA缺乏P53激活的人前列腺癌LNCaP细胞中发现的结果相反，在PANC-1细胞中诱导G2阻滞伴随着突变型P53 Ser15磷酸化的增加，P53靶点P21Cip1和GADD45的上调以及G2检查点激酶（Chk2）的激活，提示DNA损伤反应。在PANC-1细胞中，AKT磷酸化的快速抑制导致mTOR信号减少和自噬增加，从而减弱了caspase介导的凋亡执行。此外，每日口服MSeA （3 mg Se/kg体重）可显著抑制SCID小鼠皮下接种的PANC-1异种移植物的生长。免疫组织化学分析发现，msea处理的异种移植物中，p-Ser15 P53、P21Cip1、pS139-H2AX （DNA损伤反应）和caspase-3切割增加，pSer473AKT和Ki67增殖指数降低，肿瘤内血管密度降低。这些结果为进一步研究MSeA在胰腺癌治疗和/或化学预防中的作用提供了动力。
As a potential novel agent for treating pancreatic cancer, methylseleninic acid (MSeA) was evaluated in cell culture and xenograft models. Results showed that MSeA induced G1 cell cycle arrest and apoptosis in a majority of human and mouse pancreatic cancer cell lines, but G2 arrest in human PANC-1 and PANC-28 cell lines. In contrast to our previous finding in human prostate cancer LNCaP cells having a lack of P53 activation by MSeA, induction of G2 arrest in PANC-1 cells was accompanied by increased mutant P53 Ser15 phosphorylation, upregulation of P53-targets P21Cip1 and GADD45 and G2 checkpoint kinase (Chk2) activation, suggestive of DNA damage responses. A rapid inhibition of AKT phosphorylation was followed by reduced mTOR signaling and increased autophagy in PANC-1 cells attenuating caspase-mediated apoptosis execution. Furthermore, daily oral treatment with MSeA (3 mg Se/kg body weight) significantly suppressed growth of subcutaneously inoculated PANC-1 xenograft in SCID mice. Immunohistochemical analyses detected increased p-Ser15 P53, P21Cip1, pS139-H2AX (DNA damage responses) and caspase-3 cleavage and decreased pSer473AKT and Ki67 proliferative index and reduced intratumor vascular density in MSeA-treated xenograft. These results provide impetus for further research of MSeA in the therapy and/or chemoprevention of pancreatic cancer.
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影响因子：
56.9
作者：
Fang, YM;Vilella-Bach, M;Chen, J
通讯作者：
Chen, J
DOI：
10.3181/00379727-183-42424
发表时间：
1986-12-01
影响因子：
--
作者：
BIRT, DF
通讯作者：
BIRT, DF
影响因子：
2.9
作者：
BIRT, DF;JULIUS, AD;POUR, PM
通讯作者：
POUR, PM
影响因子：
4.7
作者：
Hu, HB;Jiang, C;Lü, JX
通讯作者：
Lü, JX
影响因子：
11.5
作者：
Biliran, H;Wang, Y;Liao, JD
通讯作者：
Liao, JD