Combined effects of carbon ion radiation and PARP inhibitor on non-small cell lung carcinoma cells: Insights into DNA repair pathways and cell death mechanisms.

The utilization of high linear energy transfer (LET) carbon ion (C-ion) in radiotherapy has witnessed a notable rise in managing highly metastatic, recurrent, and chemo/radio-resistant human cancers. Non-small cell lung cancer (NSCLC) presents a formidable challenge due to its chemo-resistance and aggressive nature, resulting in poor prognosis and survival rates. In a previous study, we demonstrated that the combination of C-ion with the poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib significantly mitigated metastasis in A549 cells.

p38 MAPK inhibitor SB203580 enhances anticancer activity of PARP inhibitor olaparib in a synergistic way on non-small cell lung carcinoma A549 cells.

The Poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib gives promising results against various types of cancers in clinical trials. The combination of drugs always increases therapeutic efficacy because of targeting multiple pathways of cancer progression. Our objective was to explore the potential synergistic anticancer activities of olaparib combined with p38 MAPK inhibitor (MAPKi) SB203580 on non-small cell lung carcinoma (NSCLC) A549 cells.

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

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.

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 (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 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 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 C ion in presence and absence of PARP-1 inhibition using siRNA or olaparib.