Raman spectroscopy detects metabolic signatures of radiation response and hypoxic fluctuations in non-small cell lung cancer

BMC Cancer

Andrew Jirasek¹  Alexandre G. Brolo²  Samantha J. Van Nest³  Leah M. Nicholson⁴  Mathew N. Hindi⁴  Nils Pavey⁴  Julian J. Lum⁵ 

[1] 0000 0001 2288 9830, grid.17091.3e, Department of Physics, I.K. Barber School of Arts and Sciences, University of British Columbia-Okanagan, 3187 University Way, V1V 1V7, Kelowna, BC, Canada;0000 0004 1936 9465, grid.143640.4, Department of Chemistry, University of Victoria, PO BOX 3065, V8W 3V6, Victoria, BC, Canada;0000 0004 1936 9465, grid.143640.4, Department of Physics and Astronomy, University of Victoria, PO BOX 1700 STN CSC, V8W 2Y2, Victoria, BC, Canada;Trev and Joyce Deeley Research Centre, BC Cancer, 2410 Lee Avenue, V8R 6V5, Victoria, BC, Canada;Trev and Joyce Deeley Research Centre, BC Cancer, 2410 Lee Avenue, V8R 6V5, Victoria, BC, Canada;Trev and Joyce Deeley Research Centre, BC Cancer, 2410 Lee Avenue, V8R 6V5, Victoria, BC, Canada;0000 0004 1936 9465, grid.143640.4, Department of Biochemistry and Microbiology, University of Victoria, PO BOX 1700 STN CSC, V8W 2Y2, Victoria, BC, Canada;

关键词: Raman spectroscopy;    Non-small cell lung cancer;    Hypoxia;    Reoxygenation;    Ionizing radiation;    Immunofluorescence;   

DOI  :  10.1186/s12885-019-5686-1

来源: publisher

【 摘 要 】

BackgroundRadiation therapy is a standard form of treating non-small cell lung cancer, however, local recurrence is a major issue with this type of treatment. A better understanding of the metabolic response to radiation therapy may provide insight into improved approaches for local tumour control. Cyclic hypoxia is a well-established determinant that influences radiation response, though its impact on other metabolic pathways that control radiosensitivity remains unclear.MethodsWe used an established Raman spectroscopic (RS) technique in combination with immunofluorescence staining to measure radiation-induced metabolic responses in human non-small cell lung cancer (NSCLC) tumour xenografts. Tumours were established in NOD.CB17-Prkdcscid/J mice, and were exposed to radiation doses of 15 Gy or left untreated. Tumours were harvested at 2 h, 1, 3 and 10 days post irradiation.ResultsWe report that xenografted NSCLC tumours demonstrate rapid and stable metabolic changes, following exposure to 15 Gy radiation doses, which can be measured by RS and are dictated by the extent of local tissue oxygenation. In particular, fluctuations in tissue glycogen content were observed as early as 2 h and as late as 10 days post irradiation. Metabolically, this signature was correlated to the extent of tumour regression. Immunofluorescence staining for γ–H2AX, pimonidazole and carbonic anhydrase IX (CAIX) correlated with RS-identified metabolic changes in hypoxia and reoxygenation following radiation exposure.ConclusionOur results indicate that RS can identify sequential changes in hypoxia and tumour reoxygenation in NSCLC, that play crucial roles in radiosensitivity.

【 授权许可】

CC BY