1. Department of Radiology, College of Medicine, Yonsei University, Seoul 03722, Republic of Korea;
2. Brain Korea 21 Plus Project for Medical Science, College of Medicine, Yonsei University, Seoul 03722, Republic of Korea;
3. YUHS-KRIBB Medical Convergence Research Institute, Seoul 03722, Republic of Korea;
4. Severance Biomedical Science Institute (SBSI), Seoul 03722, Republic of Korea.
Real-time screening of cellular response on the drugs could provide valuable insights for the early detection of therapeutic efficiency and the evaluation of disease progression. Cancer cells have the ability to vary widely in response to stress in a manner to adjust the signaling pathway to promote the survival or having a resistance to stimulation. Cell-based label-free technologies using electronic impedance sensor have strategies for constructing the signature profiles of each cells. To achieve exquisite sensitivity to substantially change of live-cell response have an important role that predict the potential of therapeutic effects. In this study, we use an impedance-based real-time cell analysis system to investigate dynamic phenotypes of cells described as a cellular index value. We show that gastric cancer cells generated characteristic kinetic patterns that corresponded to the treatment order of therapeutics. The kinetic feature of the cells offers insightful information that cannot be acquired from a conventional single end-point assay. Furthermore, we employ a 'sequential treatment strategy' to increase cytotoxic effects with minimizing the use of chemotherapeutics. Specifically, treatment of paclitaxel (PTX) after down-regulating Akt gene expression using RNAi reduces the cell proliferation and increases apoptosis. We propose that the sequential treatment may exhibit more effective approach rather than traditional combination therapy. Moreover, the dynamic monitoring of cell-drug interaction enables us to obtain a better understanding of the temporal effects in vitro.
Keywords: Akt, gastric cancer, paclitaxel (PTX), real-time cell analysis (RTCA), sequential treatment, small interfering RNA (siRNA).