Development of a double-layer microfluidic chip with flow medium for chemotherapy resistance analysis of lung cancer

Electrophoresis. 2011 Nov;32(23):3446-53. doi: 10.1002/elps.201100086. Epub 2011 Nov 10.

Abstract

Integration and miniaturization are main advantages of microchip-based systems. Vertical integration of the multiple operations within a multiple-layer chip is expected to satisfy the urgent demand for high-throughput and large-scale applications. This study aimed at establishing a double-layer chip to integrate the operations including the cell culture, the identification of the protein and the detection of the cell viability onto a platform systematically and supplied with flow fresh medium continuously via a syringe pump to mimic the microenvironment in vivo. With this device, human non-small cell lung cancer cell line (SPCA-1) was cultured well; the expression and the activity of multidrug resistance-associated protein (MRP1) were detected by immunofluorescence assay for the cells pretreated with or without MK-571, a known inhibitor of MRP1; apoptosis percentages were assayed for the cells after being treated by the anticancer drug etoposide (VP-16). The results demonstrated that the function of the MRP1 was inhibited by MK-571, and the percentage of apoptotic for the cells pretreated with MK-571 was higher than that of the control (38.2±2.5% versus 12.3±0.85%, p<0.005). All these indicated that the new device could provide a suitable condition for cell culture and functional analysis in biomedical research, and MK-571 is an effective inhibitor of MRP1 associated with the viability of SPCA-1 cell line treated by VP-16.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / analysis
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxorubicin / analysis
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / physiology
  • Enzyme Inhibitors / pharmacology
  • Equipment Design
  • Etoposide / pharmacology
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Microfluidic Analytical Techniques / instrumentation
  • Microfluidic Analytical Techniques / methods*
  • Microscopy, Fluorescence
  • Multidrug Resistance-Associated Proteins / antagonists & inhibitors
  • Multidrug Resistance-Associated Proteins / metabolism
  • Propionates / pharmacology
  • Quinolines / pharmacology
  • Rhodamine 123 / analysis
  • Rhodamine 123 / pharmacokinetics

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Multidrug Resistance-Associated Proteins
  • Propionates
  • Quinolines
  • Rhodamine 123
  • verlukast
  • Etoposide
  • Doxorubicin
  • multidrug resistance-associated protein 1