Reduction of metastatic potential by inhibiting EGFR/Akt/p38/ERK signaling pathway and epithelial-mesenchymal transition after carbon ion exposure is potentiated by PARP-1 inhibition in non-small-cell lung cancer

BACKGROUND: Carbon ion ((12)C) radiotherapy is becoming very promising to kill highly metastatic cancer cells keeping adjacent normal cells least affected. Our previous study shows that combined PARP-1 inhibition with (12)C ion reduces MMP-2,-9 synergistically in HeLa cells but detailed mechanism are not clear. To understand this mechanism and the rationale of using PARP-1 inhibitor with (12)C ion radiotherapy for better outcome in controlling metastasis, we investigated metastatic potential in two non-small cell lung cancer (NSCLC) A549 and H1299 (p53-deficient) cells exposed with (12)C ion in presence and absence of PARP-1 inhibition using siRNA or olaparib. METHODS: We monitored cell proliferation, in-vitro cell migration, wound healing, expression and activity of MMP-2, − 9 in A549 and p53-deficient H1299 cell lines exposed with (12)C ion with and without PARP-1 inhibitor olaparib/DPQ. Expression and phosphorylation of NF-kB, EGFR, Akt, p38, ERK was also observed in A549 and H1299 cells exposed with (12)C ion with and without PARP-1 inhibition using siRNA or olaparib. We also checked expression of few marker genes involved in epithelial-mesenchymal transition (EMT) pathways like N-cadherin, vimentin, anillin, claudin-1, − 2 in both NSCLC. To determine the generalized effect of (12)C ion and olaparib in inhibition of cell’s metastatic potential, wound healing and activity of MMP-2, − 9 was also studied in HeLa and MCF7 cell lines after (12)C ion exposure and in combination with PARP-1 inhibitor olaparib. RESULTS: Our experiments show that (12)C ion and PARP-1 inhibition separately reduces cell proliferation, cell migration, wound healing, phosphorylation of EGFR, Akt, p38, ERK resulting inactivation of NF-kB. Combined treatment abolishes NF-kB expression and hence synergistically reduces MMP-2, − 9 expressions. Each single treatment reduces N-cadherin, vimentin, anillin but increases claudin-1, − 2 leading to suppression of EMT process. However, combined treatment synergistically alters these proteins to suppress EMT pathways significantly. CONCLUSION: The activation pathways of transcription of MMP-2,-9 via NF-kB and key marker proteins in EMT pathways are targeted by both (12)C ion and olaparib/siRNA. Hence, (12)C ion radiotherapy could potentially be combined with olaparib as chemotherapeutic agent for better control of cancer metastasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-6015-4) contains supplementary material, which is available to authorized users.