Volume 40 Issue 3
Mar.  2024
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ZHANG Huilan, GUO Wenhui, SU Tingting, CHEN Si, YU Qianhui, YIN Qihang, WAN Linlu, WANG Xu, TANG Decai. Astragalus Mongholicus Bunge-Curcuma Aromatica-Paridis Rhizoma Inhibits Metastasis of Colon Cancer via the PERK/eIF2α/ATF4 Signaling Pathway[J]. Journal of Nanjing University of traditional Chinese Medicine, 2024, 40(3): 240-248. DOI: 10.14148/j.issn.1672-0482.2024.0240
Citation: ZHANG Huilan, GUO Wenhui, SU Tingting, CHEN Si, YU Qianhui, YIN Qihang, WAN Linlu, WANG Xu, TANG Decai. Astragalus Mongholicus Bunge-Curcuma Aromatica-Paridis Rhizoma Inhibits Metastasis of Colon Cancer via the PERK/eIF2α/ATF4 Signaling Pathway[J]. Journal of Nanjing University of traditional Chinese Medicine, 2024, 40(3): 240-248. DOI: 10.14148/j.issn.1672-0482.2024.0240
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Astragalus Mongholicus Bunge-Curcuma Aromatica-Paridis Rhizoma Inhibits Metastasis of Colon Cancer via the PERK/eIF2α/ATF4 Signaling Pathway

  • School of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

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  • Received Date: October 08, 2023
  • Available Online: March 14, 2024
    Graphical Abstract
    • Abstract
  •   OBJECTIVE  To investigate the mechanism of anti-colorectal cancer growth and metastasis-related effects of Astragalus mongholicus Bunge-Curcuma aromatica-Paridis Rhizoma (Qi-Zhu-Zao) pairing through PERK/eIF2α/ATF4 signaling pathway mediating endoplasmic reticulum stress.
      METHODS  Twenty-four BALB/c male mice were randomly divided into sham-operated group, model group, 5-FU (5-fluorouracil) group (25 mg·kg-1), and Qi-Zhu-Zao high dose group (5.85 g·kg-1), Qi-Zhu-Zao low dose group(2.925 g·kg-1) (n=6) to construct a mouse model of colorectal cancer in situ transplantation tumor, and the intervention effect of Qi-Zhu-Zao combination on tumor growth was assessed by the change of tumor volume size after 15 days of administration; the intervention effect of Qi-Zhu-Zao combination on tumor growth was assessed by H&E. Pathological staining was used to evaluate the effect of Qi-Zhu-Zao combination on the liver and tumor tissues of mice. The changes of MDA, SOD and GSH-Px levels were detected by enzyme-linked immunosorbent assay (ELISA); the expression of PERK/eIF2α/ATF4 signaling pathway and EMT-related proteins were detected by protein immunoblotting (Western blot).
      RESULTS  Compared with the model group, the tumor volume was significantly reduced (P < 0.000 1), liver and spleen metastases were less pronounced in the Qi-Zhu-Zao high-dose group, and histopathological staining results of liver tissue and tumor produced changes in oxidative stress indicators SOD, MDA, and GSH-Px, upregulation of ER stress-related proteins p-PERK, p-IF2α, and ATF4, etc., upregulated the protein expression levels of E-Cadherin, downregulated N-Cadherin, Vimentin, and Snail, and inhibited the EMT process (P < 0.01 or P < 0.05).
      CONCLUSION  In this paper, we investigated the regulatory mechanism related to the inhibition of colorectal cancer growth and metastasis by the combination of Qi-Zhu-Zao trigonal medicine, and demonstrated that it may inhibit the growth and metastasis of colorectal cancer by activating the PERK/eIF2α/ATF4 pathway to induce sustained ER stress and affect the EMT process of colorectal cancer.
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