학술논문

Cell-cycle fate-monitoring distinguishes individual chemosensitive and chemoresistant cancer cells in drug-treated heterogeneous populations demonstrated by real-time FUCCI imaging
Document Type
article
Source
Cell Cycle. 14(4)
Subject
Biochemistry and Cell Biology
Biological Sciences
Cancer
Antineoplastic Agents
Apoptosis
Cell Cycle
Cell Lineage
Cisplatin
Doxorubicin
HeLa Cells
Humans
Mitosis
Neoplasms
Optical Imaging
Proportional Hazards Models
Time-Lapse Imaging
cancer
cell cycle
chemoresistance
chemosensitivity
cisplatinum
doxorubicin
FUCCI
GFP
RFP
HeLa
time-lapse imaging
tumor heterogeneity
Hela Cells
Developmental Biology
Biochemistry and cell biology
Language
Abstract
Essentially every population of cancer cells within a tumor is heterogeneous, especially with regard to chemosensitivity and resistance. In the present study, we utilized the fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging system to investigate the correlation between cell-cycle behavior and apoptosis after treatment of cancer cells with chemotherapeutic drugs. HeLa cells expressing FUCCI were treated with doxorubicin (DOX) (5 μM) or cisplatinum (CDDP) (5 μM) for 3 h. Cell-cycle progression and apoptosis were monitored by time-lapse FUCCI imaging for 72 h. Time-lapse FUCCI imaging demonstrated that both DOX and CDDP could induce cell cycle arrest in S/G2/M in almost all the cells, but a subpopulation of the cells could escape the block and undergo mitosis. The subpopulation which went through mitosis subsequently underwent apoptosis, while the cells arrested in S/G2/M survived. The present results demonstrate that chemoresistant cells can be readily identified in a heterogeneous population of cancer cells by S/G2/M arrest, which can serve in future studies as a visible target for novel agents that kill cell-cycle-arrested cells.