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

Abstract

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.

Keywords:

• PARP inhibitor
• Olaparib
• Gamma radiation
• MMPs activity
• cell migration
• Epithelial–mesenchymal transition pathway

Acknowledgments

All the authors are thankful to Saha Institute of Nuclear Physics, Kolkata, India, for instrumental facility for gamma irradiation. UG thanks DST-FIST for infrastructural facilities in the Department of Biochemistry and Biophysics, University of Kalyani.

Disclosure statement

The authors declare that there are no conflicts of interests.

Additional information

Funding

UG and PD are thankful to IUAC [IUAC/XIII.7/UFR-60329] for financial support. PC thanks ICMR [BMS/FW/CMB/2015-24000/JUN-2016/05/WB/GOVT] for her senior research fellowship. DD thanks the DST for DST-INSPIRE fellowship [DST/INSPIRE Fellowship/2014/37]. UG is thankful to CSIR [37(1674)/16/EMR-II] and DBT [BT/PR 4809/BRB/10/1028/2012] for the partial financial assistance.

Notes on contributors

Priyanka Chowdhury

Priyanka Chowdhury is a Ph.D. scholar of the Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, India.

Payel Dey

Payel Dey is a Ph.D. scholar of the Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, India.

Debapriya De

Debapriya De is a Ph.D. scholar of the Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, India.