Gamma ray-induced in vitro cell migration via EGFR/ERK/Akt/p38 activation is prevented by olaparib pretreatment.

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.