Cerium Oxide Nanoparticles Sensitize Pancreatic Cancer to Radiation Therapy through Oxidative Activation of the JNK Apoptotic Pathway.
Cerium Oxide Nanoparticles Sensitize Pancreatic Cancer to Radiation Therapy through Oxidative Activation of the JNK Apoptotic Pathway.
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氧化岩纳米颗粒通过JNK凋亡途径的氧化激活使胰腺癌对放射治疗敏感。
DOI：
10.3390/cancers10090303
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发表时间：
2018-09-01
期刊：
影响因子：
5.2
通讯作者：
Zhao J
中科院分区：
文献类型：
--
作者：
Wason MS;Lu H;Yu L;Lahiri SK;Mukherjee D;Shen C;Das S;Seal S;Zhao J
Side effects of radiation therapy (RT) remain the most challenging issue for pancreatic cancer treatment. Cerium oxide nanoparticles (CONPs) are currently being tested in pre-clinical trials as an adjuvant to sensitize pancreatic cancer cells to RT and protect normal tissues from the harmful side effects. CONPs were not able to significantly affect RT-induced DNA damage in cancer cells, thereby ruling out sensitization through increased mitotic catastrophe. However, activation of c-Jun terminal kinase (JNK), a key driver of RT-induced apoptosis, was significantly enhanced by co-treatment with CONPs and RT in pancreatic cancer cells in vitro and human pancreatic tumors in nude mice in vivo compared to CONPs or RT treatment alone. Further, CONP-driven increase in RT-induced JNK activity was associated with a marked increase in Caspase 3/7 activation, indicative of apoptosis. We have previously shown that CONPs increase reactive oxygen species (ROS) production in cancer cells. ROS has been shown to drive the oxidation of thioredoxin 1 (TRX1) which results in the activation of apoptosis signaling kinase 1 (ASK1). The increase in ASK1 activation following the co-treatment with CONPs followed by RT suggests that the increased JNK activation is the result of increased TRX1 oxidation. The ability of CONPs to sensitize pancreatic cancer cells to RT was mitigated when the TRX1 oxidation was prevented by mutagenesis of a cysteine residue or when the JNK activation was blocked by an inhibitor. Taken together, these data demonstrate an important mechanism for CONPs in specifically killing cancer cells and provide novel insights into the utilization of CONPs as a radiosensitizer and therapeutic agent for pancreatic cancer.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
纳米症：一种稀土纳米颗粒，是一种新型的卵巢癌抗血管生成治疗剂。
影响因子：
3.7
作者：
Giri S;Karakoti A;Graham RP;Maguire JL;Reilly CM;Seal S;Rattan R;Shridhar V
通讯作者：
Shridhar V
影响因子：
3.7
作者：
Karakoti, A. S.;Kuchibhatla, Satyanarayana V. N. T.;Seal, S.
通讯作者：
Seal, S.
DOI：
10.1016/j.nano.2011.12.011
发表时间：
2012-10-01
影响因子：
5.4
作者：
Madero-Visbal, Rafael A.;Alvarado, Beatrice E.;Manon, Rafael
通讯作者：
Manon, Rafael
影响因子：
4.8
作者：
Lu, Heng;Hu, Liu;Zhao, Jihe
通讯作者：
Zhao, Jihe