Inhibition of Polo-like kinase 1 (PLK1) triggers cell apoptosis via ROS-caused mitochondrial dysfunction in

Ya Feng1, Tianjiao Li1, Zhoujun Lin1

  • 1State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, No. 38 Tongyan Road, Jinnan District, Tianjin, 300350, People's Republic of China.

Abstract

Insights

Polo-like kinase 1 (PLK1) inhibition reduces colorectal cancer (CRC) cell viability and migration. This study highlights PLK1 as a promising therapeutic target for CRC treatment, with BI6727 showing potential.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Colorectal cancer (CRC) is a prevalent malignancy with poorly understood non-mitotic roles of Polo-like kinase 1 (PLK1).
  • PLK1 is crucial for cell cycle regulation, including chromosome segregation, centrosome maturation, and cytokinesis.

Purpose of the Study:

  • To investigate the tumorigenic effects of PLK1 in colorectal cancer.
  • To explore the potential of PLK1 as a therapeutic target for CRC treatment.

Main Methods:

  • Utilized GEPIA database and immunohistochemistry to assess PLK1 expression in CRC.
  • Employed RNAi and the small molecule inhibitor BI6727 to inhibit PLK1.
  • Assessed cell viability, migration, apoptosis, mitochondrial membrane potential, and ROS levels using MTT, colony formation, transwell, and flow cytometry assays.
  • Evaluated PLK1 inhibition effects in preclinical models, including bioluminescence imaging and xenograft tumor models.

Main Results:

  • PLK1 was significantly accumulated in CRC tissues compared to adjacent healthy tissues.
  • PLK1 inhibition reduced CRC cell viability, migration, and colony formation, while inducing apoptosis.
  • PLK1 inhibition led to increased ROS, decreased Bcl2/Bax ratio, mitochondrial dysfunction, and Cytochrome c release, initiating apoptosis.

Conclusions:

  • PLK1 plays a significant role in CRC pathogenesis.
  • PLK1 inhibition demonstrates therapeutic potential for CRC.
  • The PLK1 inhibitor BI6727 represents a potential novel therapeutic strategy for colorectal cancer.

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