Paclitaxel inhibits proliferation by negatively regulating Cdk1-cell cycle axis in rat airway smooth muscle cells

Abstract

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.

Keywords:

• Paclitaxel
• ASMCs
• cell proliferation
• cell cycle
• Cdk1

Authors’ contributions

BX, DY, and BWM designed the research. ZHH, BX, LXL, and LXH performed the experiments. BX and LXL analyzed data and wrote the paper.

Disclosure statement

The authors report no conflict of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant Nos. 82360010, 82060006, and 81760008], Middle-aged Teachers’ Basic Research Ability Improvement Project of Universities in Guangxi [Grant No. 2023KY0541], Open Fund of Guangxi Key Laboratory of Glucose and Lipid Metabolic Diseases, Second Affiliated Hospital of Guilin Medical University [Grant No. KFKT2022001], and Innovation Project of Guangxi Graduate Education [Grant No. YCSW2023429].