Effects of paclitaxel on EGFR endocytic trafficking revealed using quantum dot tracking in single cells

PLoS One. 2012;7(9):e45465. doi: 10.1371/journal.pone.0045465. Epub 2012 Sep 20.

Abstract

Paclitaxel (PTX), a chemotherapeutic drug, affects microtubule dynamics and influences endocytic trafficking. However, the mechanism and the dynamics of altered endocytic trafficking by paclitaxel treatment in single living cells still remain elusive. By labeling quantum dots (QDs) to the epidermal growth factor (EGF), we continuously tracked the endocytosis and post-endocytic trafficking of EGF receptors (EGFRs) in A549 cells for a long time interval. A single-cell analysis method was introduced to quantitatively study the dynamics of endocytic trafficking. Compared with the control cells, the velocity of directed motion was reduced by 30% due to the suppression of high speed movements of EGF-QDs along the microtubules in PTX-treated cells. The endocytic trafficking in PTX-treated cells was mainly via super-diffusive mode of motion, whereas in control cells, it was mostly via sub-diffusive mode of motion. Moreover, PTX shortened endosomal trafficking and prevented EGF-QDs from moving to the perinuclear area via the rapid delivery of EGF-QDs into the peripheral lysosomes. The present study may shed light on the mechanism of the effect of PTX on the treatment of lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Endocytosis / drug effects*
  • Endosomes / drug effects
  • Endosomes / metabolism
  • ErbB Receptors / metabolism*
  • Humans
  • Microtubules / metabolism
  • Models, Molecular
  • Paclitaxel / pharmacology*
  • Protein Binding
  • Protein Transport / drug effects
  • Quantum Dots*
  • Single-Cell Analysis / methods*
  • Staining and Labeling
  • Tubulin Modulators / pharmacology*

Substances

  • Tubulin Modulators
  • ErbB Receptors
  • Paclitaxel

Grant support

This work was supported by the National Natural Science Foundation of China (Grant 10834014) and the National Basic Research Program of China (973 Program) (Grant 2009CB930704). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.