Palbociclib Enhances Migration and Invasion of Cancer Cells via Senescence-Associated Secretory Phenotype-Related CCL5 in Non-Small-Cell Lung Cancer

Pengzhou Kong; Xin Yang; Yingying Zhang; Huiling Dong; Xiangchen Liu; Xiaoqin Xu; Xinri Zhang; Yiwei Shi; Mingxia Hou; Bin Song

doi:10.1155/2022/2260625

Palbociclib Enhances Migration and Invasion of Cancer Cells via Senescence-Associated Secretory Phenotype-Related CCL5 in Non-Small-Cell Lung Cancer

J Oncol. 2022 Sep 27:2022:2260625. doi: 10.1155/2022/2260625. eCollection 2022.

Authors

Pengzhou Kong^{1

2}, Xin Yang¹, Yingying Zhang¹, Huiling Dong¹, Xiangchen Liu¹, Xiaoqin Xu^{1

3}, Xinri Zhang², Yiwei Shi², Mingxia Hou², Bin Song^{1

4}

Affiliations

¹ Key Laboratory of Cellular Physiology of the Ministry of Education, & Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi, China.
² Department of Respiratory and Critical Care Medicine, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi, China.
³ Department of Etiology, Shanxi Cancer Hospital, Taiyuan, Shanxi, China.
⁴ Cancer Center, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Shanxi, China.

Abstract

Palbociclib is the first CDK4/6 inhibitor approved by FDA and has been studied in many types of cancer. However, some studies showed that it could induce epithelial-mesenchymal transition (EMT) of cancer cells. To test the effect of palbociclib on non-small-cell lung cancer (NSCLC) cells, we treated NSCLC cells with different concentrations of palbociclib and detected its effects via MTT, migration and invasion assays, and apoptosis test. Further RNA sequencing was performed in the cells treated with 2 μM palbociclib or control. And Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and protein-protein interaction network (PPI) were analyzed to explore the mechanism of palbociclib. The results showed that palbociclib significantly inhibited the growth of NSCLC cells and promoted apoptosis of cells, however, enhanced the migration and invasion abilities of cancer cells. RNA sequencing showed that cell cycle, inflammation-/immunity-related signaling, cytokine-cytokine receptor interaction, and cell senescence pathways were involved in the process, and CCL5 was one of the significantly differential genes affected by palbociclib. Further experiments showed that blocking CCL5-related pathways could reverse the malignant phenotype induced by palbociclib. Our results revealed that palbociclib-induced invasion and migration might be due to senescence-associated secretory phenotype (SASP) rather than EMT and suggested that SASP could act as a potential target to potentiate the antitumor effects of palbociclib in cancer treatment.