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. 2020 Jan-Dec:19:1534735420972486.
doi: 10.1177/1534735420972486.

Inhibition to Epithelial-Mesenchymal Transition and Metastatic Potential In Colorectal Cancer Cell By Combination of Traditional Chinese Medicine Formulation Jiedu Sangen Decoction and PD-L1 Inhibitor

Feiyu Shan  1 , Leitao Sun  2 , Leyin Zhang  3 , Kaibo Guo  3 , Qingying Yan  4 , Guan Feng  3 , Ying Zhu  3 , Minhe Shen  2 , Shanming Ruan  2
Affiliations

Inhibition to Epithelial-Mesenchymal Transition and Metastatic Potential In Colorectal Cancer Cell By Combination of Traditional Chinese Medicine Formulation Jiedu Sangen Decoction and PD-L1 Inhibitor

Feiyu Shan et al. Integr Cancer Ther. 2020 Jan-Dec.

Abstract

Background: Jiedu Sangen Decoction (JSD), a traditional Chinese medicine formula, has been widely applied in the treatment of gastrointestinal cancer, especially in colorectal cancer. Our study mainly aimed to assess the combined efficacy of Jiedu Sangen aqueous extract (JSAE) and a PD-L1 inhibitor (PI) in colon cancer cells migration and invasion, along with epithelial-mesenchymal transition, and then provide deep insights into the potential mechanism.

Methods: We explored the inhibitory effects on invasion and metastasis and the reverse effect on EMT process in CT-26 colon cancer cell via Transwell migration assay, Matrigel invasion assay and confocal laser scanning microscopy. Furthermore, regulation in expression of EMT-related proteins and molecular biomarkers and underlying signal pathway proteins were detected through Western blotting and IHC.

Results: The combination of JSD and PD-L1 inhibitor could inhibit migration, invasive ability and EMT of CT-26 cells in a concentration-dependent manner. Meanwhile, JSD combined with PD-L1 inhibitor could also remarkably reverse EMT and metastasis in vivo. In addition, the protein expression of N-cadherin, Slug, Snail, Vimentin was down-regulated along with E-cadherin s up-regulation with the combination of JSD and PD-L1 inhibitor, while that of PI3K/AKT was notably down-regulated.

Conclusions: These findings indicated that JSAE and a PD-L1 inhibitor could drastically inhibit the migration and invasion of colorectal cancer by reversing EMT through the PI3K/AKT signaling pathway.

Keywords: Jiedu Sangen decoction; PI3K/AKT; colorectal cancer; epithelial-mesenchymal transition; metastasis.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
JSD combined with PD-L1 inhibitor reverse EMT in vitro. (a) The expression of E-cadherin, N-cadherin and β-actin were measured by CLSM. (b) The expression of EMT-related proteins in CT-26 cell were measured by Western blotting assay.
Figure 2.
Figure 2.
JSD combined with PD-L1 inhibitor inhibits migratory and invasive ability of CT-26 cells. (a, c) The migration ability of CT-26 cells in relevant groups was detected by Transwell Assay. (b, d) The invasive ability of CT-26 cells in relevant groups was detected by Matrigel assay. Compared to EGF group, ▼P < .05; Compared to JP group, △P < .05.
Figure 3.
Figure 3.
Survival curves of mice (12 mice per group) with metastatic tumor formed by CT-26 cells in relevant groups.
Figure 4.
Figure 4.
JSD combined with PD-L1 inhibitor inhibits EMT and metastasis in vivo. (a, b) The expression of E-cadherin and N-cadherin in mouse liver tissues was measured by IHC. (c) The expression of EMT-related proteins in mouse liver tissues was measured by Western blotting assay. (d) The difference of mouse liver size in relevant groups. Compared to EGF group, ▼P < .05; Compared to JP group, △P < .05.
Figure 5.
Figure 5.
JSD combined with PD-L1 inhibitor may inhibit EMT via PI3K/AKT signaling pathway. (a) The discrepant expression of proteins related to PI3K/AKT signaling pathway in CT-26 cells. (b) The discrepant expression of proteins related to PI3K/AKT signaling pathway in mouse liver tissues.
See this image and copyright information in PMC

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