Gamma ray-induced in vitro cell migration via EGFR/ERK/Akt/p38 activation is prevented by olaparib pretreatment
Gamma ray-induced in vitro cell migration via EGFR/ERK/Akt/p38 activation is prevented by olaparib pretreatment
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DOI：
10.1080/09553002.2020.1711461
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发表时间：
2020-02-06
影响因子：
2.6
通讯作者：
Ghosh, Utpal
中科院分区：
文献类型：
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作者：
Chowdhury, Priyanka;Dey, Payel;Ghosh, Utpal
目的：伽玛射线放射治疗仍是各种癌症的主要治疗手段。然而，放疗后局部复发和转移增加仍然是一个主要的治疗挑战。本工作的目的是检测三种不同的人癌细胞在伽玛射线联合PARP抑制剂olaparib照射后，细胞迁移以及参与上皮-间充质转化(EMT)途径的一些标志性蛋白的活性和表达。材料和方法：我们研究了三种高转移人癌细胞A549、HeLa和U2OS在伽玛射线照射后的细胞存活率、体外细胞迁移、明胶酶谱检测MMPs的活性、少数EMT标志物蛋白的表达以及MMPs转录调控的信号级联。结果：我们观察到单纯的伽玛射线照射可增加三种细胞的体外迁移、基质金属蛋白酶-2、-9活性、N-钙粘蛋白、波形蛋白的表达以及信号分子EGFR、ERK1/2、Akt、p38的表达，从而增强三种细胞中的NF-kB的表达。单独应用奥拉帕利可减少细胞在体外的迁移，同时减少上述EMT途径标记蛋白的表达。然而，奥拉帕利预处理4h可阻止伽玛射线诱导的所有这些标记蛋白在所有三种细胞类型中的激活。结论：这一数据暗示奥拉帕利联合伽马治疗在保护患者免受伽马诱导的转移方面可能是有前景的。
Purpose: Radiotherapy using gamma ray is still the main therapeutic modality for the treatment of various cancers. However, local recurrence and increase of metastasis after radiotherapy is still a major therapeutic challenge. Aim of this work was to check cell migration along with activity and expression of some marker proteins involved in epithelial-mesenchymal transition (EMT) pathway in three different human cancer cells after exposure with gamma radiation in combination with PARP inhibitor olaparib. Materials and methods: Here, we presented cell viability, in vitro cell migration, activity of MMPs by gelatin zymography, expression of few EMT marker proteins and the signaling cascade involved in transcriptional regulation of MMPs after gamma irradiation with and without olaparib pretreatment in highly metastatic three human cancer cell lines-A549, HeLa and U2OS. Results: We observed that gamma irradiation alone increased in vitro cell migration, MMP-2,-9 activity, expression of N-cadherin, vimentin and the signaling molecules EGFR, ERK1/2, Akt, p38 that enhanced NF-kB expression in all three cell types. Olaparib treatment alone reduced in vitro cell migration along with reduction of expression of all the above-mentioned marker proteins of the EMT pathway. However, 4 h olaparib pretreatment prevented gamma ray induced activation of all these marker proteins in all three cell types. Conclusions: This data implicates that olaparib treatment in combination with gamma therapy could be promising in protecting patients from gamma-induced metastasis.