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Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Analysis of drug action on tumor cell metabolism using electronic sensor chips
Angela M Otto1, Martin Brischwein, Elena Motrescu
1Heinz-Nixdorf-Chair for Medical Electronics, Technical University of Munich, Munich, Germany. otto@tum.de
Abstract:
Chemotherapeutic drugs affect the metabolism of tumor cells regardless of the specific target of action. Basic parameters of cell metabolism are extrusion of acids into the microenvironment and oxygen consumption. To analyze these changes on living cells in real-time, a test system based on multiparametric chips with an array of sensors for monitoring pH and O(2) as well as electric impedance has been developed. Cells are cultivated on these chips and supplied with medium by a fluid perfusion set-up which mimics microphysiological conditions and allows for drug addition and removal. Human colon carcinoma cells LS174T were used as a model to test the effect of drugs. Cells growing on chips were monitored for 24 h and longer. Untreated cells showed a continuous increase in the rate of acidification, while the rate of respiration remained fairly constant. Addition of chloroacetaldehyde (50 microM) rapidly attenuated O(2) consumption with a gradual decrease in acidification following. In contrast, with cisplatin (16.7 microM) a delayed and gradual decrease in both the rates of acidification and respiration effect occurred over 2-3 days. These results provide insights to the mechanisms of action of these drugs, which are coherent with those already known. Thus, multiparametric sensor chips provide elementary information on drug action.
Insights
Multiparametric sensor chips monitor real-time changes in tumor cell metabolism, including acidification and oxygen consumption. This system reveals distinct real-time effects of chemotherapeutic drugs like chloroacetaldehyde and cisplatin on cancer cell metabolism.
Area of Science:
- Biomedical Engineering
- Cancer Research
- Cellular Metabolism
Background:
- Chemotherapeutic drugs significantly impact tumor cell metabolism, affecting key parameters like acid extrusion and oxygen consumption.
- Real-time analysis of these metabolic changes in living cells is crucial for understanding drug mechanisms.
Purpose of the Study:
- To develop and validate a novel multiparametric sensor chip system for real-time monitoring of tumor cell metabolism.
- To investigate the effects of specific chemotherapeutic agents on cancer cell metabolic activity.
Main Methods:
- Development of a microfluidic chip system with integrated sensors for real-time monitoring of pH, oxygen (O(2)), and electric impedance.
- Cultivation of human colon carcinoma LS174T cells on the sensor chips under microphysiological conditions.
- Real-time measurement of cellular acidification and respiration rates following drug administration.
Main Results:
- Untreated LS174T cells exhibited a consistent increase in acidification rate and a stable respiration rate.
- Chloroacetaldehyde (50 µM) rapidly reduced oxygen consumption and subsequently decreased acidification.
- Cisplatin (16.7 µM) induced a delayed, gradual decrease in both acidification and respiration rates over 2-3 days.
Conclusions:
- Multiparametric sensor chips offer a powerful tool for real-time, in-depth analysis of chemotherapeutic drug effects on cancer cell metabolism.
- The observed distinct metabolic responses to chloroacetaldehyde and cisplatin align with known drug mechanisms, validating the system's utility.
- This technology provides fundamental insights into drug action, aiding in the development and evaluation of cancer therapies.
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