WRH-2412 alleviates the progression of hepatocellular carcinoma through regulation of TGF-β/β-catenin/α-SMA pathway

References

• (a) Pisaturo M, Di Fraia A, Occhiello L, Minichini C, Starace M, Iodice V, et al. Genetic Variability in Patients with HCV-Related Hepatocellular Carcinoma. Infect Drug Resist. 2021; 14:5199–5208.
   PubMed Web of Science ®Google Scholar
  (b) Kuchuk O, Tuccitto A, Citterio D, Huber V, Camisaschi C, Milione M, Vergani B, et al. pH regulators to target the tumor immune microenvironment in human hepatocellular carcinoma. Oncoimmunology. 2018;7(7):e1445452.
   PubMed Web of Science ®Google Scholar
• Zucman-Rossi J, Villanueva A, Nault JC, Llovet JM. Genetic landscape and biomarkers of hepatocellular carcinoma. Gastroenterology. 2015; 149(5):1226–1239 e1224.
   PubMed Web of Science ®Google Scholar
• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1):7–30.
   PubMed Web of Science ®Google Scholar
• (a) Sun Y, Tang H, Wang X, Feng F, Fan T, Zhao D, Xiong B, Xie H, Liu T. Identification of 1 H-pyrazolo [3, 4-b] pyridine derivatives as novel and potent TBK1 inhibitors: design, synthesis, biological evaluation, and molecular docking study. J Enzyme Inhib Med Chem. 2022;37(1):1411–1425.
   PubMedGoogle Scholar
  (b) Eissa IH, El-Naggar AM, El-Hashash MA. Design, synthesis, molecular modeling and biological evaluation of novel 1H-pyrazolo [3, 4-b] pyridine derivatives as potential anticancer agents. Bioorg Chem. 2016;67:43–56.
   PubMed Web of Science ®Google Scholar
• (a) Liu N, Wang X, Fu Q, Qin Q, Wu T, Lv R, Zhao D, Cheng M. Design, synthesis and biological evaluation of pyrazolo [3, 4-b] pyridine derivatives as TRK inhibitors. RSC Med Chem. 2023;14:85–102;
   PubMedGoogle Scholar
  (b) Park A, Hwang J, Lee J-Y, Heo EJ, Na Y-J, Kang S, Jeong K-S, Kim KY, Shin SJ, Lee H. Synthesis of novel 1H-Pyrazolo [3, 4-b] pyridine derivatives as DYRK 1A/1B inhibitors. Bioorg Med Chem Lett. 2021;47:128226.
   PubMed Web of Science ®Google Scholar
• El-Gohary NS, Gabr MT, Shaaban MI. Synthesis, molecular modeling and biological evaluation of new pyrazolo[3,4-b]pyridine analogs as potential antimicrobial, antiquorum-sensing and anticancer agents. Bioorg Chem. 2019; 89:102976.
   PubMed Web of Science ®Google Scholar
• Mohamed LW, Shaaban MA, Zaher AF, Alhamaky SM, Elsahar AM. Synthesis of new pyrazoles and pyrozolo [3,4-b] pyridines as anti-inflammatory agents by inhibition of COX-2 enzyme. Bioorg Chem. 2019;83:47–54.
   PubMed Web of Science ®Google Scholar
• Gouda MA. Synthesis and antioxidant evaluation of some new pyrazolopyridine derivatives. Arch Pharm. 2012;345(2):155–162.
   PubMed Web of Science ®Google Scholar
• Barghash RF, Eldehna WM, Kovalova M, Vojackova V, Krystof V, Abdel-Aziz HA. One-pot three-component synthesis of novel pyrazolo[3,4-b]pyridines as potent antileukemic agents. Eur J Med Chem. 2022;227:113952.
   PubMed Web of Science ®Google Scholar
• Zhang H-F, Gao X, Wang X, Chen X, Huang Y, Wang L, Xu Z-W. The mechanisms of renin-angiotensin system in hepatocellular carcinoma: From the perspective of liver fibrosis, HCC cell proliferation, metastasis and angiogenesis, and corresponding protection measures. Biomed Pharmacother. 2021;141:111868.
   PubMed Web of Science ®Google Scholar
• Thompson MD, Monga SP. WNT/beta-catenin signaling in liver health and disease. Hepatology. 2007;45(5):1298–1305.
   PubMed Web of Science ®Google Scholar
• El-Far YM, Khodir AE, Emarah ZA, Ebrahim MA, Al-Gayyar MMH. Chemopreventive and hepatoprotective effects of genistein via inhibition of oxidative stress and the versican/PDGF/PKC signaling pathway in experimentally induced hepatocellular carcinoma in rats by thioacetamide. Redox Rep. 2022;27(1):9–20.
   PubMed Web of Science ®Google Scholar
• Yang Y, Sun M, Yao W, Wang F, Li X, Wang W, et al. Compound kushen injection relieves tumor-associated macrophage-mediated immunosuppression through TNFR1 and sensitizes hepatocellular carcinoma to sorafenib. J Immunother Cancer. 2020;8(1):e000317.
   Google Scholar
• Elsherbiny NM, Al-Gayyar MM. Anti-tumor activity of arjunolic acid against Ehrlich ascites carcinoma cells in vivo and in vitro through blocking TGF-beta type 1 receptor. Biomed Pharmacother. 2016;82:28–34.
   PubMed Web of Science ®Google Scholar
• Qu Z, Feng J, Pan H, Jiang Y, Duan Y, Fa Z. Exosomes derived from HCC cells with different invasion characteristics mediated EMT through TGF-beta/Smad signaling pathway. Onco Targets Ther. 2019;12:6897–6905.
   PubMed Web of Science ®Google Scholar
• Tajul Arifin K, Sulaiman S, Md Saad S, Ahmad Damanhuri H, Wan Ngah WZ, Mohd Yusof YA. Elevation of tumour markers TGF-beta, M2-PK, OV-6 and AFP in hepatocellular carcinoma (HCC)-induced rats and their suppression by microalgae Chlorella vulgaris. BMC Cancer. 2017;17(1):879.
   PubMedGoogle Scholar
• Xu Y, Yu X, Sun Z, He Y, Guo W. Roles of lncRNAs mediating Wnt/beta-catenin signaling in HCC. Front Oncol. 2022;12:831366.
   PubMed Web of Science ®Google Scholar
• Jemal A, Center MM, DeSantis C, Ward EM. Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomarkers Prev. 2010;19(8):1893–1907.
   PubMed Web of Science ®Google Scholar
• Dedes KJ, Wetterskog D, Mendes-Pereira AM, Natrajan R, Lambros MB, Geyer FC, Vatcheva R, Savage K, Mackay A, Lord CJ, et al. PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors. Sci Transl Med. 2010;2(53):53ra75.
   PubMed Web of Science ®Google Scholar
• Huang DS, Liu TT, Lu WT, Wang CC, Lin CC, Yong CC, et al. Comparison of portal and capsular microscopic vascular invasion in the outcomes of early HCC after curative resection. Am J Cancer Res. 2022;12(6):2659–2672.
   PubMed Web of Science ®Google Scholar
• Shi M, Zhang CQ, Zhang YQ, Liang XM, Li JQ. Micrometastases of solitary hepatocellular carcinoma and appropriate resection margin. World J Surg. 2004;28(4):376–381.
   PubMed Web of Science ®Google Scholar
• Zhang X, Li J, Shen F, Lau WY. Significance of presence of microvascular invasion in specimens obtained after surgical treatment of hepatocellular carcinoma. J Gastroenterol Hepatol. 2018;33(2):347–354.
   PubMed Web of Science ®Google Scholar
• Elewa MA, Al-Gayyar MM, Schaalan MF, Abd El Galil KH, Ebrahim MA, El-Shishtawy MM. Hepatoprotective and anti-tumor effects of targeting MMP-9 in hepatocellular carcinoma and its relation to vascular invasion markers. Clin Exp Metastasis. 2015;32(5):479–493.
   PubMed Web of Science ®Google Scholar
• Alshehri MA, Alshehri MM, Albalawi NN, Al-Ghamdi MA, Al-Gayyar MMH. Heparan sulfate proteoglycans and their modification as promising anticancer targets in hepatocellular carcinoma. Oncol Lett. 2021;21(2):173.
   PubMed Web of Science ®Google Scholar
• Zhan S, Liu Z, Zhang M, Guo T, Quan Q, Huang L, Guo L, Cao L, Zhang X. Overexpression of B7-H3 in alpha-SMA-positive fibroblasts is associated with cancer progression and survival in gastric adenocarcinomas. Front Oncol. 2019;9:1466.
   PubMed Web of Science ®Google Scholar
• Hashiguchi M, Ueno S, Sakoda M, Iino S, Hiwatashi K, Minami K, Ando K, Mataki Y, Maemura K, Shinchi H, et al. Clinical implication of ZEB-1 and E-cadherin expression in hepatocellular carcinoma (HCC). BMC Cancer. 2013;13:572.
   PubMed Web of Science ®Google Scholar