Gentiopicroside suppresses cell proliferation, migration, and invasion via inhibition of the HGF/PI3K/Akt pathway in clear cell renal cell carcinoma
References
- A. Deleuze, J. Saout, F. Dugay, B. Peyronnet, R. Mathieu, G. Verhoest, K. Bensalah, L. Crouzet, B. Laguerre, M. A. Belaud-Rotureau, N. Rioux-Leclercq and S. F. Kammerer-Jacquet, Immunotherapy in renal cell carcinoma: The future is now, Int. J. Mol. Sci. 21(7) (2020) Article ID 2532 (22 pages); https://doi.org/10.3390/ijms21072532
- R. L. Siegel, T. B. Kratzer, A. N. Giaquinto, H. Sung and A. Jemal, Cancer statistics, 2025, CA Cancer J. Clin. 75(1) (2025) 10–45; https://doi.org/10.3322/caac.21871
- U. Capitanio and F. Montorsi, Renal cancer, Lancet 387(10021) (2016) 894–906; https://doi.org/10.1016/s0140-6736(15)00046-x
- P. Makhov, S. Joshi, P. Ghatalia, A. Kutikov, R. G. Uzzo and V. M. Kolenko, Resistance to systemic therapies in clear cell renal cell carcinoma: Mechanisms and management strategies, Mol. Cancer Therapeutics 17(7) (2018) 1355–1364; https://doi.org/10.1158/1535-7163.mct-17-1299
- J. W. Yang, K. S. Wang and Z. C. Yang, Treatment strategies for clear cell renal cell carcinoma: Past, present and future, Front. Oncol. 13 (2023) Article ID 1133832 (16 pages); https://doi.org/10.3389/fonc.2023.1133832
- Y. J. Guo, P. Gao, W. Deng and S. J. Wang, Doxorubicin-induced chronic heart failure is alleviated by gentiopicroside by inhibiting oxidative stress and inflammation, Ind. J. Pharm. Educ. Res. 57(3) (2023) 890–897; https://doi.org/10.5530/ijper.57.3.107
- X. H. Li, C. L. Yang and H. Shen, Gentiopicroside exerts convincing antitumour effects in human ovarian carcinoma cells (SKOV3) by inducing cell cycle arrest, mitochondrial mediated apoptosis and inhibition of cell migration, J. Buon. 24(1) (2019) 280–284.
- Q. S. Chen, T. T. Zhang, B. J. Li, Z. G. Zhu, X. M. Ma, Y. Zhang, L. C. Li, J. K. Zhu and G.Y. Zhang, Gentiopicroside inhibits the progression of gastric cancer through modulating EGFR/PI3K/AKT signaling pathway, Eur. J. Med. Res. 29(1) (2024) Article ID 47 (14 pages); https://doi.org/10.1186/s40001-024-01637-6
- Y. Yang, J. N. He, S. J. Jin and L. Chen, Bax/Bcl-2 and caspase 3 pathway-mediated apoptosis induced by gentiopicroside in human colorectal cancer cells, J. Clin. Oncol. 36(15) (2018) Article ID e15665-e15665; https://doi.org/10.1200/JCO.2018.36.15_suppl.e15665
- C. Xue, G. L. Li, J. Lu and L. J. Li, Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression, Signal Transduc. Target. Ther. 6(1) (2021) Article ID 400 (17 pages); https://doi.org/10.1038/s41392-021-00788-w
- J. Y. Yin, F. Zhang, J. M. Cao, Z. C. C. Chen and W. Xiong, Gentiopicroside inhibits retinoblastoma cell proliferation, invasion, and tumourigenesis in nude mice by suppressing the PI3K/AKT pathway, Naunyn-Schmiedebergs Arch. Pharmacol. 397(2) (2024) 1003–1013; https://doi.org/10.1007/s00210-023-02646-8
- H. L. Zhang, Q. Q. Feng, W. D. Chen and Y. D. Wang, HGF/c-MET: A promising therapeutic target in the digestive system cancers, Int. J. Mol. Sci. 19(11) (2018) Article ID 3295 (17 pages); https://doi.org/10.3390/ijms19113295
- L. Gesualdi, E. Leonetti, A. Cucina, B. M. Scicchitano, S. Sorrentino, M. G. Tarsitano, A. Isidori, M. Bizzarri, A. Filippini, A. Riccioli, M. Cammarota, V. Gigantino, G. Ricci and A. Catizone, The PI3K/AKT pathway is activated by HGF in NT2D1 non-seminoma cells and has a role in the modulation of their malignant behavior, Int. J. Mol. Sci. 21(22) (2020) Article ID 8669 (21 pages); https://doi.org/10.3390/ijms21228669
- N. Guo, J. W. Liang, X. Gao, X. Yang, X. L. Fan and Y. J. Zhao, Overexpressed HGF promotes meta-stasis of squamous cell carcinoma of the head and neck through the PI3K/Akt and JNK signaling pathways, Fut. Oncol. 17(33) (2021) 4527–4543; https://doi.org/10.2217/fon-2020-1207
- W. B. Kuang, Q. C. Deng, C. T. Deng, W. S. Li, S. W. Shu and M. R. Zhou, Hepatocyte growth factor induces breast cancer cell invasion via the PI3K/Akt and p38 MAPK signaling pathways to up-regulate the expression of COX2, Am. J. Translat. Res. 9(8) (2017) 3816–3826
- J. H. Kim, K. H. Hwang, S. Lkhagvadorj, J. H. Jung, H. C. Chung, K. S. Park, I. D. Kong, M. Eom and S. K. Cha, Klotho plays a critical role in clear cell renal cell carcinoma progression and clinical outcome, Kor. J. Physiol. Pharmacol. 20(3) (2016) 297–304; https://doi.org/10.4196/kjpp.2016.20.3.297
- C. Lv, X. T. Wu, X. Wang, J. Su, H. W. Zeng, J. Zhao, S. Lin, R. H. Liu, H. L. Li, X. Li and W. D. Zhang, The gene expression profiles in response to 102 traditional Chinese medicine (TCM) components: A general template for research on TCMs, Sci. Rep. 7 (2017) Article ID 352 (10 pages); https://doi.org/10.1038/s41598-017-00535-8
- G. Stelzer, N. Rosen, I. Plaschkes, S. Zimmerman, M. Twik, S. Fishilevich, T. I. Stein, R. Nudel, I. Lieder, Y. Mazor, S. Kaplan, D. Dahary, D. Warshawsky, Y. Guan-Golan, A. Kohn, N. Rappaport, M. Safranm and D. Lancet, The GeneCards suite: From gene data mining to disease genome sequence analyses, Curr. Protoc. Bioinform. 54 (2016) Article ID 1.30.1-1.30.33; https://doi.org/10.1002/cpbi.5
- P. Bardou, J. Mariette, F. Escudié, C. Djemiel and C. Klopp, jvenn: An interactive Venn diagram viewer, BMC Bioinform. 15 (2014) Article ID 293 (7 pages); https://doi.org/10.1186/1471-2105-15-293
- B. T. Sherman, M. Hao, J. Qiu, X. L. Jiao, M. W. Baseler, H. C. Lane, T. Imamichi and W. Z. Chang, DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update), Nucleic Acids Res. 50(W1) (2022) W216-W221; https://doi.org/10.1093/nar/gkac194
- K. J. Livak and T. D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔCT method, Methods 25(4) (2001) 402–408; https://doi.org/10.1006/meth.2001.1262
- H. Tian, L. Liu, T. J. Yang and Y. Q. Wang, Gentiopicroside inhibits cancer cell growth in OVCAR-3 ovary cancer cells through the mediation of apoptosis, loss of mitochondrial transmembrane potential and NF-kB signalling pathway, Biomed. Res. India 27(2) (2016) 413–418
- B. Xiong, M. J. Fan, Z. H. Wang, X. L. Yang, S. Cao, J. Shen and B. B. Fan, Gentiopicroside-induced gastric cancer necroptosis via the HIF-1 signaling pathway: A study involving molecular docking and experimental validation, PloS one 19(11) (2024) e0311152; https://doi.org/10.1371/journal.pone.0311152
- H. M. Xiao, X. H. Sun, Z. Y. Lin, Y. Yang, M. Zhang, Z. C. Xu, P. Q. Liu, Z. Q. Liu and H. Q. Huang, Gentiopicroside targets PAQR3 to activate the PI3K/AKT signaling pathway and ameliorate disordered glucose and lipid metabolism, Acta Pharm. Sin. B 12(6) (2022) 2887–2904; https://doi.org/10.1016/j.apsb.2021.12.023
- S. P. Xing, F. F. Nong, J. L. Qin, H. C. Huang, R. T. Zhan and W. W. Chen, Gentiopicroside produces endothelium-independent vasodilation by deactivating the PI3K/Akt/Rho-kinase pathway in isolated rat thoracic aorta, Biomed. Res. Int. 2021 (2021) Article ID 5565748 (10 pages); https://doi.org/10.1155/2021/5565748
- Z. Q. Xie, Y. H. Lee, M. Boeke, L. B. Jilaveanu, Z. Z. Liu, D. P. Bottaro, H. M. Kluger and B. Shuch, MET inhibition in clear cell renal cell carcinoma, J. Cancer 7(10) (2016) 1205–1214; https://doi.org/10.7150/jca.14604
Language: English
Accepted on: Oct 11, 2026
Published on: Oct 26, 2026
Published by: Croatian Pharmaceutical Society
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year
Keywords:
Related subjects:
© 2026 Xiaoling Wang, Zhijie Song, Nannan Zhang, Chunyan Zhang, Chunying Bai, Xianjun Liu, published by Croatian Pharmaceutical Society
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.