ArticleJournal of cellular and molecular medicine2021
AANG: A natural compound formula for overcoming multidrug resistance via synergistic rebalancing the TGF-β/Smad signalling in hepatocellular carcinoma.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Kaempferide in Alpinia officinarum Hance Exerts Anti-Hepatocellular Carcinoma Activity by Inhibiting Mitophagy Through Downregulation of BNIP3L.Journal of cellular and molecular medicine · 2026Article
- Naringenin, a Food-Derived Flavanone, Suppresses ITGA11-Associated Gastric Cancer Progression via the FAK/PI3K/AKT/mTOR Axis.Cancers · 2026Article
- Metabolomic profiles and health-promoting potential ofFrontiers in plant science · 2025Article
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Editorial: New insights into fibrotic signaling in cancer.Frontiers in oncology · 2024Article
- Advance in Targeted Cancer Therapy and Mechanisms of Resistance.International journal of molecular sciences · 2023Article
- [Research progress on the mechanism and response strategies of molecular targeted drug resistance in liver cancer].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023Article
- TGF-β as A Master Regulator of Aging-Associated Tissue Fibrosis.Aging and disease · 2023Review
- Modulation of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment by Natural Products.Archivum immunologiae et therapiae experimentalis · 2023Review
- Tumour-associated macrophages: versatile players in the tumour microenvironment.Frontiers in cell and developmental biology · 2023Review
- Frontier progress of the combination of modern medicine and traditional Chinese medicine in the treatment of hepatocellular carcinoma.Chinese medicine · 2022Review
- LncRNA-Dependent Mechanisms of Transforming Growth Factor-β: From Tissue Fibrosis to Cancer Progression.Non-coding RNA · 2022Review
- Traditional Chinese medicine reverses cancer multidrug resistance and its mechanism.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- AANG Prevents Smad3-dependent Diabetic Nephropathy by Restoring Pancreatic β-Cell Development in db/db Mice.International journal of biological sciences · 2022Article
- Smad3 Promotes Cancer-Associated Fibroblasts Generation via Macrophage-Myofibroblast Transition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- AANG: A natural compound formula for overcoming multidrug resistance via synergistic rebalancing the TGF-β/Smad signalling in hepatocellular carcinoma.Journal of cellular and molecular medicine · 2021Article
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells are high in heterogeneity and versatility, which can easily adapt to the external stresses via both primary and secondary resistance. Targeting of tumour microenvironment (TME) is a new approach and an ideal therapeutic strategy especially for the multidrug resistant cancer. Recently, we invented AANG, a natural compound formula containing traditional Chinese medicine (TCM) derived Smad3 inhibitor Naringenin (NG) and Smad7 activator Asiatic Acid (AA), for rebalancing TGF-β/Smad signalling in the TME, and its implication on the multidrug resistance is still unexplored. Here, we observed that an equilibrium shift of the Smad signalling in patients with hepatocellular carcinoma (HCC), which was dramatically enhanced in the recurrent cases showing p-glycoprotein overexpression. We optimized the formula ratio and dosage of AANG that effectively inhibit the proliferation of our unique human multidrug resistant subclone R-HepG2. Mechanistically, we found that AANG not only inhibits Smad3 at post-transcriptional level, but also upregulates Smad7 at transcriptional level in a synergistic manner in vitro. More importantly, AANG markedly suppressed the growth and p-glycoprotein expression of R-HepG2 xenografts in vivo. Thus, AANG may represent a novel and safe TCM-derived natural compound formula for overcoming HCC with p-glycoprotein-mediated multidrug resistance.
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