Inhibition of aquaporins as a potential adjunct to breast cancer cryotherapy.
Inhibition of aquaporins as a potential adjunct to breast cancer cryotherapy.
复制标题
抑制水通道蛋白作为乳腺癌冷冻治疗的潜在辅助手段。
DOI：
10.3892/ol.2021.12719
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发表时间：
2021-06
期刊：
影响因子：
2.9
通讯作者：
Fredericks S
中科院分区：
文献类型：
--
作者：
Alkhalifa H;Mohammed F;Taurin S;Greish K;Taha S;Fredericks S
冷冻消融是一种新兴的癌症治疗方法。在治疗前使用冷冻增敏剂对肿瘤进行增敏可以提高消融效率，并可能改善临床结果。由水通道蛋白通道调节的水外排有助于通过冷冻消融实现癌细胞损伤。水通道蛋白（AQP） 3的增加具有低温保护作用，而其抑制则会增加低温损伤。本研究旨在探讨低温损伤对水通道蛋白（AQP1、AQP3和AQP5）基因表达和细胞定位的影响。将培养的乳腺癌细胞（MDA-MB-231和MCF-7）冷冻诱导冷冻损伤。然后分别用逆转录定量PCR和western blotting分析RNA和蛋白质提取物。用免疫细胞化学方法研究水通道蛋白的定位。此外，用小干扰RNA转染细胞以沉默水通道蛋白基因表达，并使用Sulforhodamine B法评估细胞活力。除了MDA-MD-231细胞中AQP1的表达增加4倍外，冷冻损伤对AQPs的基因表达没有影响。MCF-7细胞在冰冻温度和非冰冻温度下AQP蛋白表达无明显差异，但非冰冻温度下MCF-7细胞AQP蛋白表达较弱。癌细胞暴露在冰冻温度下改变了MCF-7和MDA-MD-231细胞中AQP1和AQP3蛋白的定位。与对照siRNA相比，AQP1、AQP3和AQP5的沉默加重了与冷冻相关的MDA-MD-231细胞损伤。MCF-7细胞中AQP3和AQP5的沉默也观察到这一点。抑制水通道蛋白可能潜在地增强低温损伤。这种冷冻增敏过程可以作为乳腺癌冷冻治疗的辅助手段，特别是在冷冻消融靶向的边缘区域，那里的冷冻温度不够冷，无法诱导细胞损伤。
Cryoablation is an emerging type of treatment for cancer. The sensitization of tumors using cryosensitizing agents prior to treatment enhances ablation efficiency and may improve clinical outcomes. Water efflux, which is regulated by aquaporin channels, contributes to cancer cell damage achieved through cryoablation. An increase in aquaporin (AQP) 3 is cryoprotective, whereas its inhibition augments cryodamage. The present study aimed to investigate aquaporin (AQP1, AQP3 and AQP5) gene expression and cellular localization in response to cryoinjury. Cultured breast cancer cells (MDA-MB-231 and MCF-7) were exposed to freezing to induce cryoinjury. RNA and protein extracts were then analyzed using reverse transcription-quantitative PCR and western blotting, respectively. Localization of aquaporins was studied using immunocytochemistry. Additionally, cells were transfected with small interfering RNA to silence aquaporin gene expression and cell viability was assessed using the Sulforhodamine B assay. Cryoinjury did not influence gene expression of AQPs, except for a 4-fold increase of AQP1 expression in MDA-MD-231 cells. There were no clear differences in AQP protein expression for either cell lines upon exposure to frozen and non-frozen temperatures, with the exception of fainter AQP5 bands for non-frozen MCF-7 cells. The exposure of cancer cells to freezing temperatures altered the localization of AQP1 and AQP3 proteins in both MCF-7 and MDA-MD-231 cells. The silencing of AQP1, AQP3 and AQP5 exacerbated MDA-MD-231 cell damage associated with freezing compared with control siRNA. This was also observed with AQP3 and AQP5 silencing in MCF-7 cells. Inhibition of aquaporins may potentially enhance cryoinjury. This cryosensitizing process may be used as an adjunct to breast cancer cryotherapy, especially in the border area targeted by cryoablation where freezing temperatures are not cold enough to induce cellular damage.
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影响因子：
5.2
作者：
Ahmad, Ayah E.;Khajah, Maitham A.;Luqmani, Yunus A.
通讯作者：
Luqmani, Yunus A.
影响因子：
2.9
作者：
Fujita, Y;Yamamoto, N;Asai, K
通讯作者：
Asai, K
影响因子：
3.1
作者：
Baust, John G.;Snyder, Kristi K.;Baust, John M.
通讯作者：
Baust, John M.
影响因子：
2.7
作者：
Clarke, DM;Baust, JM;Baust, JG
通讯作者：
Baust, JG
影响因子：
2.6
作者：
Beji, Hedi;Pilleul, Frank;Mastier, Charles
通讯作者：
Mastier, Charles