Acquired tumor cell radiation resistance at the treatment site is mediated through radiation-orchestrated intercellular communication.
Acquired tumor cell radiation resistance at the treatment site is mediated through radiation-orchestrated intercellular communication.
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DOI：
10.1016/j.ijrobp.2013.11.215
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发表时间：
2014-03-01
影响因子：
7
通讯作者：
Natarajan, Mohan
中科院分区：
文献类型：
--
作者：
Aravindan, Natarajan;Aravindan, Sheeja;Pandian, Vijayabaskar;Khan, Faizan H.;Ramraj, Satish Kumar;Natt, Praveen;Natarajan, Mohan
放射治疗（RT）后存活的癌细胞诱导的放射耐药可能与辐射保护增加有关，限制了辐射的治疗益处。在此，我们研究了辐射诱导肿瘤细胞辐射保护的顺序机制分子协调。无论是低剂量辐照（LDIR）范围（10,50或100 cGy）还是更高的激发剂量辐照（CDIR）， 4gy，都会诱导剂量依赖性和持续的nf - κ b - dna结合活性。然而，当细胞在攻毒剂量前被LDIR激活时，cdir诱导的NFκB活性显著增加，DNA片段化减少，细胞凋亡减少，细胞毒性和cdir抑制克隆扩增的减弱。此外，通过小干扰RNA （siRNA）沉默或p50/p65过表达对NFκB的操纵研究揭示了ldir激活的NFκB在调节cdir诱导的DNA片段化和细胞凋亡中的作用。LDIR显著增加了肿瘤坏死因子-α (TNF- α)、白细胞介素-1α (IL-1α)、cMYC和SOD2的反激活/翻译。共培养实验显示，ldir影响辐射保护，增加细胞表达，分泌，以及旁观者细胞中辐射反应分子的激活。sirna的个体基因沉默方法与共培养研究表明，ldir调节的TNF- α、IL-1α、cMYC和SOD2对诱导的旁观者细胞辐射保护有影响。nf - κ b抑制/过表达研究结合共培养实验表明，ldir诱导的nf - κ b可选择性调节TNF- α、IL-1 α、cMYC和SOD2。总之，这些数据有力地表明，分散的ldir诱导的nfκ b依赖性TNF-α、IL-1α、cMYC和SOD2介导肿瘤细胞对随后的攻击剂量的辐射保护。
Radiation resistance induced in cancer cells that survive after radiation therapy (RT) could be associated with increased radiation protection, limiting the therapeutic benefit of radiation. Herein we investigated the sequential mechanistic molecular orchestration involved in radiation-induced radiation protection in tumor cells. Radiation, both in the low-dose irradiation (LDIR) range (10, 50, or 100 cGy) or at a higher, challenge dose IR (CDIR), 4 Gy, induced dose-dependent and sustained NFκB-DNA binding activity. However, a robust and consistent increase was seen in CDIR-induced NFκB activity, decreased DNA fragmentation, apoptosis, and cytotoxicity and attenuation of CDIR-inhibited clonal expansion when the cells were primed with LDIR prior to challenge dose. Furthermore, NFκB manipulation studies with small interfering RNA (siRNA) silencing or p50/p65 overexpression unveiled the influence of LDIR-activated NFκB in regulating CDIR-induced DNA fragmentation and apoptosis. LDIR significantly increased the transactivation/translation of the radiation-responsive factors tumor necrosis factor-α (TNF- α), interleukin-1 α (IL-1α), cMYC, and SOD2. Coculture experiments exhibit LDIR-influenced radiation protection and increases in cellular expression, secretion, and activation of radiation-responsive molecules in bystander cells. Individual gene-silencing approach with siRNAs coupled with coculture studies showed the influence of LDIR-modulated TNF- α, IL-1α, cMYC, and SOD2 in induced radiation protection in bystander cells. NFκB inhibition/overexpression studies coupled with coculture experiments demonstrated that TNF- α, IL-1 α, cMYC, and SOD2 are selectively regulated by LDIR-induced NFκB. Together, these data strongly suggest that scattered LDIR-induced NFκB-dependent TNF-α, IL-1α, cMYC, and SOD2 mediate radiation protection to the subsequent challenge dose in tumor cells.
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影响因子：
2.9
作者：
Veeraraghavan, Jamunarani;Natarajan, Mohan;Aravindan, Natarajan
通讯作者：
Aravindan, Natarajan
影响因子：
4.8
作者：
Veeraraghavan, Jamunarani;Natarajan, Mohan;Aravindan, Natarajan
通讯作者：
Aravindan, Natarajan
影响因子：
2.9
作者：
Madhusoodhanan, Rakhesh;Natarajan, Mohan;Aravindan, Natarajan
通讯作者：
Aravindan, Natarajan
影响因子：
2
作者：
Madhusoodhanan, Rakhesh;Natarajan, Mohan;Aravindan, Natarajan
通讯作者：
Aravindan, Natarajan
影响因子：
4
作者：
Aravindan, Natarajan;Mohan, Sumathy;Natarajan, Mohan
通讯作者：
Natarajan, Mohan