The Roles of HIF-1α in Radiosensitivity and Radiation-Induced Bystander Effects Under Hypoxia.
The Roles of HIF-1α in Radiosensitivity and Radiation-Induced Bystander Effects Under Hypoxia.
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HIF-1 α 在缺氧条件下放射敏感性和辐射引起的旁观者效应中的作用
DOI：
10.3389/fcell.2021.637454
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发表时间：
2021
影响因子：
5.5
通讯作者：
Prise KM
中科院分区：
文献类型：
--
作者：
Zhang J;Zhang Y;Mo F;Patel G;Butterworth K;Shao C;Prise KM
放射诱导的旁观者效应(RIBE)可能对放射治疗有潜在的影响，但其对低氧肿瘤细胞的放射生物学影响和潜在机制仍有待确定。以人肝癌细胞株HepG2和胶质母细胞瘤细胞株T98G为研究对象，发现在常氧和低氧条件下，未照射的旁观者细胞与X射线照射细胞共培养或用X射线照射细胞条件培养液处理后，其微核形成率增加，细胞存活率降低。虽然低氧肿瘤细胞的辐射敏感性低于有氧细胞，但旁观者细胞在低氧条件下诱发的微核率与常氧条件下测得的微核率相近，表明RIBE在低氧细胞的整体辐射损伤中是一个更重要的因素。当低氧细胞在照射前和照射期间分别用活性氧(ROS)清除剂二甲基亚砜(DMSO)或一氧化氮合酶(NOS)抑制剂氨基胍(AG)处理时，旁观者反应部分减弱。此外，仅用siRNA缺氧诱导因子-1α(HIF-1α)处理低氧旁观者细胞时，RIBE略有下降，而用siRNA HIF-1α处理后，低氧RIBE显著降低。此外，低氧诱导因子-1α的表达与其他下游效应分子如葡萄糖转运蛋白1、血管内皮细胞生长因子和碳酸氢酶等协同作用。而同基因照射细胞条件培养液可降低旁观者细胞HIF-1α的表达。结果表明，在低氧条件下，照射后的肝癌细胞HIF-1α表达增加，放射敏感性降低；HIF-1α表达降低，其下游靶基因表达下调，从而诱导同基因旁观者效应。
Radiation-induced bystander effects (RIBE) may have potential implications for radiotherapy, yet the radiobiological impact and underlying mechanisms in hypoxic tumor cells remain to be determined. Using two human tumor cell lines, hepatoma HepG2 cells and glioblastoma T98G cells, the present study found that under both normoxic and hypoxic conditions, increased micronucleus formation and decreased cell survival were observed in non-irradiated bystander cells which had been co-cultured with X-irradiated cells or treated with conditioned-medium harvested from X-irradiated cells. Although the radiosensitivity of hypoxic tumor cells was lower than that of aerobic cells, the yield of micronucleus induced in bystander cells under hypoxia was similar to that measured under normoxia indicating that RIBE is a more significant factor in overall radiation damage of hypoxic cells. When hypoxic cells were treated with dimethyl sulfoxide (DMSO), a scavenger of reactive oxygen species (ROS), or aminoguanidine (AG), an inhibitor of nitric oxide synthase (NOS), before and during irradiation, the bystander response was partly diminished. Furthermore, when only hypoxic bystander cells were pretreated with siRNA hypoxia-inducible factor-1α (HIF-1α), RIBE were decreased slightly but if irradiated cells were treated with siRNA HIF-1α, hypoxic RIBE decreased significantly. In addition, the expression of HIF-1α could be increased in association with other downstream effector molecules such as glucose transporter 1 (GLUT-1), vascular endothelial growth factor (VEGF), and carbonic anhydrase (CA9) in irradiated hypoxic cells. However, the expression of HIF-1α expression in bystander cells was decreased by a conditioned medium from isogenic irradiated cells. The current results showed that under hypoxic conditions, irradiated HepG2 and T98G cells showed reduced radiosensitivity by increasing the expression of HIF-1α and induced a syngeneic bystander effect by decreasing the expression of HIF-1α and regulating its downstream target genes in both the irradiated or bystander cells.
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影响因子：
11.2
作者：
Lorimore, Sally A.;Chrystal, Jennifer A.;Wright, Eric G.
通讯作者：
Wright, Eric G.
DOI：
10.1073/pnas.1320243111
发表时间：
2014-02-18
影响因子：
11.1
作者：
Ahn, G-One;Seita, Jun;Brown, J. Martin
通讯作者：
Brown, J. Martin
影响因子：
2.3
作者：
Clara, Carlos Afonso;Marie, Suely K. N.;Rosemberg, Sergio
通讯作者：
Rosemberg, Sergio
影响因子：
5.2
作者：
Mayer A;Schneider F;Vaupel P;Sommer C;Schmidberger H
通讯作者：
Schmidberger H
影响因子：
51.1
作者：
Formenti, Silvia C.;Demaria, Sandra
通讯作者：
Demaria, Sandra