| Autor: |
Druzhkova I; Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia., Komarova A; Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia.; Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia., Nikonova E; Laboratory of Clinical Biophotonics, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia., Baigildin V; Institute of Chemistry, Saint-Petersburg State University, 198504 St. Petersburg, Russia., Mozherov A; Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia., Shakirova Y; Institute of Chemistry, Saint-Petersburg State University, 198504 St. Petersburg, Russia., Lisitsa U; Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia., Shcheslavskiy V; Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia., Ignatova N; Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia., Shirshin E; Laboratory of Clinical Biophotonics, Sechenov First Moscow State Medical University (Sechenov University), 119991 Moscow, Russia.; Faculty of Physics, Lomonosov Moscow State University, 119991 Moscow, Russia., Shirmanova M; Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia., Tunik S; Institute of Chemistry, Saint-Petersburg State University, 198504 St. Petersburg, Russia. |
| Abstrakt: |
The extracellular matrix (ECM), in which collagen is the most abundant protein, impacts many aspects of tumor physiology, including cellular metabolism and intracellular pH (pHi), as well as the efficacy of chemotherapy. Meanwhile, the role of collagen in differential cell responses to treatment within heterogeneous tumor environments remains poorly investigated. In the present study, we simultaneously monitored the changes in pHi and metabolism in living colorectal cancer cells in vitro upon treatment with a chemotherapeutic combination, FOLFOX (5-fluorouracil, oxaliplatin and leucovorin). The pHi was followed using the new pH-sensitive probe BC-Ga-Ir, working in the mode of phosphorescence lifetime imaging (PLIM), and metabolism was assessed from the autofluorescence of the metabolic cofactor NAD(P)H using fluorescence lifetime imaging (FLIM) with a two-photon laser scanning microscope. To model the ECM, 3D collagen-based hydrogels were used, and comparisons with conventional monolayer cells were made. It was found that FOLFOX treatment caused an early temporal intracellular acidification (reduction in pHi), followed by a shift to more alkaline values, and changed cellular metabolism to a more oxidative state. The presence of unstructured collagen markedly reduced the cytotoxic effects of FOLFOX, and delayed and diminished the pHi and metabolic responses. These results support the observation that collagen is a factor in the heterogeneous response of cancer cells to chemotherapy and a powerful regulator of their metabolic behavior. |
