OBJECTIVE To explore the effect of Astragali Radix-Curcuma Zedoaria-Paridis Rhizoma (Qi-Zhu-Zao) combination on inhibiting the growth and metastasis of colon cancer based on the PINK1/Parkin/EMT signaling pathway.
METHODS Thirty male BALB/c mice were randomly assigned to five groups: sham operation group, model group, positive control group, high-dose Qi-Zhu-Zao group (5.85 g ·kg-1), and low-dose Qi-Zhu-Zao group (2.925 g ·kg-1), with six mice in each group. An orthotopic colon cancer model was established in the mice using CT26.WT cells. After 15 days of treatment, tumor and liver tissues were collected from each group. Hematoxylin and eosin (HE) staining was performed to assess tumor metastasis, and transmission electron microscopy was used to observe mitochondrial autophagy in tumor tissues. The expression of mitochondrial autophagy-related proteins PINK1, Parkin, p62, and LC3-Ⅱ/LC3-Ⅰ was analyzed using Western blot and immunohistochemistry (IHC). Additionally, the expression levels of epithelial-mesenchymal transition (EMT)-related proteins and mRNA, including E-cadherin, N-cadherin, Vimentin, and Snail, were detected using Western blot, qPCR, and IHC staining.
RESULTS Compared to the model group, mice in the treatment groups exhibited significantly reduced tumor volumes and fewer metastatic foci. Additionally, liver tissues showed pathological changes, and the overall growth condition of the mice was markedly improved; the tumor tissues in the treatment groups displayed selective mitochondrial autophagy, accompanied by the formation of autophagosomes. The treatment influenced the PINK1/Parkin pathway-mediated mitochondrial autophagy biological process, with PINK1, Parkin, p62, and LC3-Ⅱ/LC3-Ⅰ levels being significantly upregulated (P < 0.05, P < 0.01), the high-dose group exhibited a more significant impact than the low-dose group(P < 0.05, P < 0.01). Furthermore, the treatment groups also showed significant reductions in the protein and mRNA levels of N-cadherin, Vimentin, and Snail (P < 0.05, P < 0.01), along with significant increases in the protein and mRNA levels of E-cadherin (P < 0.05, P < 0.01), these effects were more pronounced in the high-dose group compared to the low-dose group(P < 0.05, P < 0.01).
CONCLUSION The herbal combination of Qi-Zhu-Zao inhibits tumor growth and metastasis to a certain extent in a mouse model of orthotopic transplantation of colon cancer. The underlying mechanism may involve the restoration of mitochondrial function through the PINK1/Parkin signaling pathway and the inhibition of the epithelial-mesenchymal transition (EMT) process, thereby achieving a therapeutic effect on colon cancer.
DownLoad: