2. Academic Validation
  3. Pharmacological inhibition of PLK1/PRC1 triggers mitotic catastrophe and sensitizes lung cancers to chemotherapy

Pharmacological inhibition of PLK1/PRC1 triggers mitotic catastrophe and sensitizes lung cancers to chemotherapy

  • Cell Death Dis. 2025 May 12;16(1):374. doi: 10.1038/s41419-025-07708-8.
Pingping Li # 1,  Yufei Zhao # 1,  Minghan Lu # 1,  Chengfei Chen # 1,  Yongkun Li 1,  Lingling Wang 2,  Shulan Zeng 1,  Yan Peng 1,  Hong Liang 1,  Guohai Zhang 3 4
Affiliations

Affiliations

  • 1 Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China.
  • 2 School of Comprehensive Health Management, Xihua University, Chengdu, China.
  • 3 Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, China. zgh1207@gxnu.edu.cn.
  • 4 Joint Medical Research Center of Guangxi Normal University & Guilin Hospital of Chinese Traditional and Western Medicine, Guilin, China. zgh1207@gxnu.edu.cn.
  • # Contributed equally.
PMID: 40355412 DOI: 10.1038/s41419-025-07708-8
Abstract

Polo-like kinase 1 (PLK1) signaling drives tumor malignancy and chemotherapy resistance, which is an unmet clinical need. Recruiting PLK1 to the central spindle during anaphase is necessary for its function in promoting Cancer cell proliferation, which is achieved by binding to microtubule-associated protein regulating of cytokinesis (PRC1) located in the spindle. However, the role of PLK1/PRC1 signaling in chemotherapy resistance is unknown. In this study, we identified a small molecule B4 which inhibited PLK1/PRC1 signaling through disrupting the formation of PLK1/PRC1 protein complexes. In the presence of blocking PLK1/PRC1 signaling, enhanced sensitivity of drug-resistant tumors to traditional chemotherapy was found. Suppression of PLK1 activity by B4 inhibited disease progression in allograft models, and combination with cisplatin elicited dramatic regression of drug-resistant tumors. Our findings provide a promising strategy to target the PLK1 signaling cascade and demonstrate a potential modality to enhance sensitivity to chemotherapy in non-small cell lung Cancer (NSCLC).

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