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. 2024 Jan 15;86(3):1376-1385.
doi: 10.1097/MS9.0000000000001629. eCollection 2024 Mar.

Polyphyllin Ⅲ regulates EMT of lung cancer cells through GSK-3β/β-catenin pathway

Qian Liu  1 , Zhuang Luo  1 , Jiao Yang  1
Affiliations

Polyphyllin Ⅲ regulates EMT of lung cancer cells through GSK-3β/β-catenin pathway

Qian Liu et al. Ann Med Surg (Lond). .

Abstract

Background: Some studies have found that the application of traditional Chinese medicine in the treatment of lung cancer has achieved satisfying results. Polyphyllin Ⅲ (PP Ⅲ) is a natural steroid saponin from P. polyphylla var. yunnanensis, and its analogs have played a wide role in anticancer research. This study aimed to investigate the effect of PP Ⅲ on the development of lung cancer and its molecular mechanism.

Methods: A549 and NCI-H1299 cell lines were treated with PP Ⅲ in gradient concentration to detect the IC50 of the cells, and the optimal concentration was selected for subsequent experiments. The effects of PP III treatment on lung cancer were investigated in vitro and in vivo.

Results: In vitro experiments, it was found that the proliferation, invasion, migration, and colony formation ability of cancer cells were significantly reduced after PP III treatment, while accompanied by a large number of cell apoptosis. Further detection showed that N-cadherin was significantly decreased, E-cadherin was increased, and Snail and Twist were decreased in A549 cells and NCI-H1299 cells, respectively. In addition, GSK-3β expression was increased, while β-catenin expression was reduced with PP III treatment. In the mouse model, it was demonstrated that the volume of transplanted tumors was significantly reduced after PP Ⅲ treatment.

Conclusions: PP Ⅲ has the capacity to inhibit the progression of lung cancer and regulate epithelial-mesenchymal transition through the GSK-3β/β-catenin pathway to suppress the malignant behavior of cancer cells. The application of PP Ⅲ is expected to be an effective method for the treatment of lung cancer.

Keywords: EMT; GSK-3β/β-catenin; Polyphyllin Ⅲ; lung cancer.

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Conflict of interest statement

The authors declare that there is no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Figures

None
Graphical abstract
Figure 1
Figure 1
The proliferation and apoptosis of lung cancer cells with PP Ⅲ treatment. A: Detection of IC50 for A549 and NIC-H1299 by CCK-8; B: Detection of proliferation activity of A549 and NIC-H1299 by CCK-8; C: The clone formation of A549 and NIC-H1299; D: The apoptosis rates of A549 and NIC-H1299 with PP Ⅲ treatment.
Figure 2
Figure 2
PP Ⅲ inhibited the malignant activity of A549 and NIC-H1299 cells. A: PP Ⅲ inhibited the invasion of lung cancer cells; B: The migration ability of lung cancer cells decreased; C-D: Related proteins expression of A549 and NIC-H1299 cells. (compared with A549: *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001; compared with NIC-H1299: # P<0.05, ## P<0.01, ### P<0.001, #### P<0.0001).
Figure 3
Figure 3
PP Ⅲ inhibited EMT of lung cancer cells through GSKβ/βcatenin pathway. A-B: The expressions of GSKβ, βcatenin, Bax and Bcl-2 in A549 and NCI-H1299 cells; C: E-Cadherin was tested by immunofluorescence assay. (compared with control group: *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001).
Figure 4
Figure 4
PP Ⅲ inhibited the growth of transplanted tumors in a mouse model. A-B: Growth of transplanted tumor volume and weight in mice; C: Pictures of A549 cell transplantation tumor in each group; D-E: Immunohistochemical staining detection of transplanted tumor markers Ki67; F-G: Expression levels of E-cadherin, N-cadherin, GSK-3β and β-catenin. (*P<0.05, **P<0.01, ***P<0.001, ****P<0.0001).
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