2. Academic Validation
  3. Polyphyllin I enhances the anti-tumor efficacy of Palbociclib by reversing M2 macrophage polarization in lung cancer

Polyphyllin I enhances the anti-tumor efficacy of Palbociclib by reversing M2 macrophage polarization in lung cancer

  • Biochem Biophys Res Commun. 2025 Jun 18:777:152228. doi: 10.1016/j.bbrc.2025.152228.
Yulan Jiang 1,  Lu Wang 2,  Yu Chen 3,  Ying Li 4,  Guanping Chen 5,  Yingyan Lu 5,  Cheng Jiang 5,  Kequn Chai 6,  Yifan Wang 7
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, China; Cancer Institute of Integrative Medicine, Zhejiang Key Laboratory of Disease-Syndrome Integration for Cancer Prevention and Treatment, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China.
  • 2 Cancer Institute of Integrative Medicine, Zhejiang Key Laboratory of Disease-Syndrome Integration for Cancer Prevention and Treatment, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China; School of Public Health, Hangzhou Medical College, Hangzhou, China.
  • 3 Cancer Institute of Integrative Medicine, Zhejiang Key Laboratory of Disease-Syndrome Integration for Cancer Prevention and Treatment, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China; School of Pharmacy, Hangzhou Normal University, Hangzhou, China.
  • 4 Department of Pharmacy, Tongde Hospital of Zhejiang Province, Hangzhou, China; Tongde Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
  • 5 Cancer Institute of Integrative Medicine, Zhejiang Key Laboratory of Disease-Syndrome Integration for Cancer Prevention and Treatment, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China; Tongde Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
  • 6 School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, China; Cancer Institute of Integrative Medicine, Zhejiang Key Laboratory of Disease-Syndrome Integration for Cancer Prevention and Treatment, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China; Tongde Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: ckqmzygzs@163.com.
  • 7 School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, China; Cancer Institute of Integrative Medicine, Zhejiang Key Laboratory of Disease-Syndrome Integration for Cancer Prevention and Treatment, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang Province, Hangzhou, China; School of Public Health, Hangzhou Medical College, Hangzhou, China; Tongde Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China. Electronic address: yifan.wang11@foxmail.com.
PMID: 40578288 DOI: 10.1016/j.bbrc.2025.152228
Abstract

Lung Cancer is a significant hazard to human health, with limited treatment options. Although CDK4/6 inhibitors like Palbociclib (Palb) have shown clinical promise, their effectiveness is often compromised by resistance. Our findings indicate that the Palb may promote M2-like macrophage polarization, which can facilitate tumor progression through immunosuppression. This study investigates the effect of Polyphyllin I (PPI) in counteracting Palb-induced M2 macrophage polarization and explored its synergistic anti-tumor potential when combined with Palb. In vitro, a macrophage polarization model showed that Palb enhanced the expression of M2 macrophage markers, which could be reversed by PPI. LLC cells were cultured with macrophage-conditioned medium (CM) showed that the PPI and Palb combination-CM group exhibited decreased proliferation, migration, and invasion capabilities in LLC cells and inhibited epithelial-mesenchymal transition (EMT) compared to the Palb-CM group. Moreover, the combination of PPI and Palb also enhanced anti-tumor effect in vivo. Mechanistically, the JAK-STAT pathway was enriched, and key signaling proteins associated with macrophage polarization, including TWEAK, p-JAK1 and p-STAT1, were significantly upregulated in the PPI-treated group. PPI can reverse Palb-induced M2 polarization by activating the TWEAK/JAK1/STAT1 signaling pathway, which can enhance the anti-tumor efficacy of Palb. These findings support PPI as a potential adjunct to CDK4/6 inhibitors for lung Cancer therapy.

Keywords

Lung cancer; Macrophage; PPI; Palb; Polarization.

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