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Published on: May 14, 2016
Paclitaxel inhibits proliferation by negatively regulating Cdk1-cell cycle axis in rat airway smooth muscle cells
Bo Xiao1,2,3,4, Zhiheng Huang2,3, Liangxian Li5
1Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Guilin Medical University, Guilin, China.
Objective:
Paclitaxel exhibits outstanding biological activities in inhibiting cell proliferation and inducing cell apoptosis. However, the effects of paclitaxel on airway smooth muscle cells (ASMCs) have not been reported yet. The purpose of this study is to determine the effects of paclitaxel on the proliferation and apoptosis of ASMCs.
Methods:
Rat primary ASMCs were isolated and used in all the experiments. Cell Counting Kit-8 assay and Edu assay were used to analyze the cell viability and proliferation, respectively. Flow cytometry was used to detect the cell cycle and apoptosis. Quantitative real-time PCR (qRT-PCR), western blotting, and immunostaining were used to detect the expression of cyclin-dependent kinase 1 (Cdk1).
Results:
Our study showed that paclitaxel inhibits the proliferation of ASMCs in a dose- and time-gradient-dependent manner. Further study displayed that cell cycle is arrested at G2/M phase. And Cdk1 was dramatically down-regulated by paclitaxel treatment. Cell morphological analysis showed that ASMCs are elliptical with a larger surface area after paclitaxel treatment. Nucleus morphological analysis showed that the nuclei are in a diffuse state after paclitaxel treatment. However, paclitaxel did not induce the apoptosis of ASMCs.
Conclusions:
Our study demonstrated that paclitaxel inhibits the proliferation of ASMCs at least partly by negatively regulating Cdk1-cell cycle axis.
Insights
Paclitaxel inhibits airway smooth muscle cell proliferation by arresting the cell cycle at G2/M phase and down-regulating Cdk1. This study reveals paclitaxel
Area of Science:
- Cell Biology
- Pharmacology
Background:
- Paclitaxel is known for its anti-proliferative and apoptosis-inducing effects.
- The impact of paclitaxel on airway smooth muscle cells (ASMCs) remains unexplored.
Purpose of the Study:
- To investigate the effects of paclitaxel on ASMC proliferation and apoptosis.
- To elucidate the underlying molecular mechanisms, including cell cycle regulation and Cdk1 expression.
Main Methods:
- Primary rat ASMCs were utilized.
- Cell Counting Kit-8 and Edu assays assessed proliferation.
- Flow cytometry analyzed cell cycle and apoptosis.
- qRT-PCR, Western blotting, and immunostaining evaluated Cdk1 expression.
Main Results:
- Paclitaxel inhibited ASMC proliferation in a dose- and time-dependent manner.
- Cell cycle arrest at the G2/M phase was observed.
- Paclitaxel treatment led to decreased Cdk1 expression.
- No significant induction of ASMC apoptosis was detected.
Conclusions:
- Paclitaxel inhibits ASMC proliferation.
- This inhibition is partly mediated by the negative regulation of the Cdk1-cell cycle axis.
- Paclitaxel does not induce apoptosis in ASMCs.
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