Disulfiram Alone Functions as a Radiosensitizer for Pancreatic Cancer Both In Vitro and In Vivo.
Disulfiram Alone Functions as a Radiosensitizer for Pancreatic Cancer Both In Vitro and In Vivo.
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双硫仑单独作为体外和体内胰腺癌的放射增敏剂
DOI：
10.3389/fonc.2021.683695
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发表时间：
2021
影响因子：
4.7
通讯作者：
Jiao Y
中科院分区：
文献类型：
--
作者：
Xu Y;Lu L;Luo J;Wang L;Zhang Q;Cao J;Jiao Y
全世界范围内胰腺癌的预后仍然很差，部分原因是早期症状缺乏特异性和对化疗/放射治疗的先天抵抗力。双硫兰(DSF)是临床上广泛使用的一种抗酒精中毒药物，几十年来一直以与铜离子同时应用时的抗肿瘤作用而闻名，包括胰腺癌。然而，关于DSF单独治疗胰腺癌的抗肿瘤作用及其相关机制，特别是其作为癌症放射治疗增敏剂的潜在作用，仍存在争议。在目前的研究中，我们重点研究DSF是否以及如何促进电离辐射(IR)以消除胰腺癌。在体外和体内，单独的DSF显著抑制了暴露于IR后的胰腺癌细胞的存活。此外，DSF单独治疗导致胰腺癌细胞DNA双链断裂(DSB)，并进一步增强IR诱导的DSB。此外，DSF单独作用可促进IR诱导的胰腺癌细胞G2/M期阻滞和细胞凋亡。RNA测序和生物信息学分析结果表明，DSF可触发细胞黏附分子(CAM)信号转导，可能参与其调节胰腺癌细胞放射敏感性的作用。综上所述，我们认为DSF可能单独作为胰腺癌的放射增敏剂，可能通过调节IR诱导的DNA损伤、细胞周期停滞和细胞凋亡，至少部分通过CAM信号通路发挥作用。
The prognosis of pancreatic cancer remains very poor worldwide, partly due to the lack of specificity of early symptoms and innate resistance to chemo-/radiotherapy. Disulfiram (DSF), an anti-alcoholism drug widely used in the clinic, has been known for decades for its antitumor effects when simultaneously applied with copper ions, including pancreatic cancer. However, controversy still exists in the context of the antitumor effects of DSF alone in pancreatic cancer and related mechanisms, especially in its potential roles as a sensitizer for cancer radiotherapy. In the present study, we focused on whether and how DSF could facilitate ionizing radiation (IR) to eliminate pancreatic cancer. DSF alone significantly suppressed the survival of pancreatic cancer cells after exposure to IR, both in vitro and in vivo. Additionally, DSF treatment alone caused DNA double-strand breaks (DSBs) and further enhanced IR-induced DSBs in pancreatic cancer cells. In addition, DSF alone boosted IR-induced cell cycle G2/M phase arrest and apoptosis in pancreatic cancer exposed to IR. RNA sequencing and bioinformatics analysis results suggested that DSF could trigger cell adhesion molecule (CAM) signaling, which might be involved in its function in regulating the radiosensitivity of pancreatic cancer cells. In conclusion, we suggest that DSF alone may function as a radiosensitizer for pancreatic cancer, probably by regulating IR-induced DNA damage, cell cycle arrest and apoptosis, at least partially through the CAM signaling pathway.
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影响因子：
--
作者：
Jiao Y;Hannafon BN;Zhang RR;Fung KM;Ding WQ
通讯作者：
Ding WQ
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
21.3
作者：
Ilina O;Gritsenko PG;Syga S;Lippoldt J;La Porta CAM;Chepizhko O;Grosser S;Vullings M;Bakker GJ;Starruß J;Bult P;Zapperi S;Käs JA;Deutsch A;Friedl P
通讯作者：
Friedl P
影响因子：
14.9
作者：
The Gene Ontology Consortium
通讯作者：
The Gene Ontology Consortium
影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
Yamanishi Y