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Volume 2 Issue 2
Apr.  2022
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Article Navigation >  Frigid Zone Medicine  > 2022  >  2(2): 119-128
Zhiyu Li, Kegong Chen, Chao Cui, Yinghui Wang, Dequan Wu. Cryptotanshinone increases the sensitivity of liver cancer to sorafenib by inhibiting the STAT3/Snail/epithelial mesenchymal transition pathway[J]. Frigid Zone Medicine, 2022, 2(2): 119-128. doi: 10.2478/fzm-2022-0016
Citation: Zhiyu Li, Kegong Chen, Chao Cui, Yinghui Wang, Dequan Wu. Cryptotanshinone increases the sensitivity of liver cancer to sorafenib by inhibiting the STAT3/Snail/epithelial mesenchymal transition pathway[J]. Frigid Zone Medicine, 2022, 2(2): 119-128. doi: 10.2478/fzm-2022-0016
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Cryptotanshinone increases the sensitivity of liver cancer to sorafenib by inhibiting the STAT3/Snail/epithelial mesenchymal transition pathway

doi: 10.2478/fzm-2022-0016
  • 1.

    Department of Liver Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China

  • 2.

    Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China

  • 3.

    Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China

  • 4.

    Department of Gastrointestinal Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou 341099, China

  • 5.

    Department of Physical Examination Center, The Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China

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    Abstract
  •   Objective  Sorafenib resistance has been a major factor limiting its clinical use as a targeted drug in liver cancer. The present study aimed to investigate whether cryptotanshinone can enhance the sensitivity of liver cancer and reduce the resistance to sorafenib.  Methods  Sorafenib-resistant cells were established based on HepG2 and Huh7 cell lines. And the anti-tumor effect of sorafenib combined with cryptotanshinone on the sorafenib-resistant cells was verified by MTT, colony formation, transwell assays and tumor growth xenograft model. Moreover, the effects of the combined treatment on the expression of phosphorylated (p)-STAT3, as well as epithelial mesenchymal transition (EMT) and apoptosis related proteins of cells were evaluated by western blot analysis.  Results  It was identified that cryptotanshinone inhibited the viability of both HepG2 and Huh7 cells in a dose- and time-dependent manner, and decreased p-STAT3 expression rather than total STAT3 expression at a concentration of 40 njmol/L. In the sorafenib-resistant cells, sorafenib in combination with cryptotanshinone markedly inhibited cell viability, invasion and migration compared with sorafenib alone. In contrast, increased p-STAT3 level by colivelin led to the inhibition of the synergistic effect of cryptotanshinone and sorafenib not only on cell viability, but also on EMT and apoptosis, suggesting that cryptotanshinone and sorafenib may act by downregulating STAT3 signaling. Further, the inhibition of carcinogenicity effect was also verified in xenografted tumor models.  Conclusion  The present results indicated that cryptotanshinone could synergize with sorafenib to inhibit the proliferative, invasive, and migratory abilities of sorafenib-resistant cells by downregulating STAT3 signaling.

     

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