Inhibitory effect of wogonin on human colorectal cancer cell SW480 based on network pharmacology

LI Yan-ping1 GONG Yi-ting1 WANG Jia-xin2 CHENG Ya-ru2 ZHANG Xin1 WANG Jing1 XU Wen-juan2 DONG Ling1

(1.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China 100029)
(2.School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China 100029)
【Knowledge Link】esophageal cancer; scaffold protein

【Abstract】Wogonin is a main effective component of Radix Scutellariae, with a significant anti-cancer activity. Recently, extensive studies have focused on the anti-cancer pharmacological effects of wogonin, but there were still a few studies on its molecular mechanism. Therefore, the molecular targets of its anti-cancer activity were still unclear. In this study, network pharmacology was applied to investigate the potential targets and molecular pathway of wogonin in inhibiting the growth of colorectal cancer. It indicated that Wnt/β-catenin was a key pathway of wogonin on colorectal cancer. Then, studies on pharmacology and molecular mechanism were performed according to network pharmacological results. Pharmacological results revealed that wogonin inhibited significantly the proliferation of SW480 (P < 0.001), with concentration-dependent regularity in the range of 12.5–50 μmol·L−1. Additionally, wogonin could arrest SW480 cells in G1 phase. Western blot was used to investigate the effect of wogonin on four characteristic proteins of Wnt/β-catenin pathway. CTNNB1 (β-catenin), BIRC5 (survivin) and GSK3B were down-regulated significantly, while the expression level of BAX was up-regulated (P < 0.05). In conclusion, wogonin could inhibit the proliferation of SW480 cells through the Wnt/β-catenin pathway. The characteristic proteins CTNNB1 (β-catenin), BIRC5 (survivin), GSK3B and BAX were identified as the potential targets. This study illuminated the anti-cancer molecular mechanism and drug targets of wogonin, which provided a theoretical basis for anti-colon cancer drug discovery and clinical application.

【Keywords】 wogonin; colorectal cancer; network pharmacology; Wnt/β-catenin pathway;


【Funds】 National Natural Science Foundation of China (81703947) Special Funding Project for Fundamental Scientific Research of Central Universities (2019-JYB-XJSJJ-011)

Download this article


    [1] WENG R N, MA J P. 关注大肠癌 [J]. World Science, 2015 (7): 20 (in Chinese).

    [2] ZHANG J X, YANG Z R, WU D D, et al. Suppressive effect of sinomenine combined with 5-fluorouracil on colon carcinoma cell growth [J]. Asian Pac J Cancer Prev, 2014, 15 (16): 6737.

    [3] SUN W W, DOU J X, ZHANG L, et al. Killing effect of Huaier combined with DC-CIK on nude mice bearing colon cancer HT29 stem cells in vivo [J]. China Journal of Chinese Materia Medica, 2018, (01): 168 (in Chinese).

    [4] CUI Y H, FU Y Q, LI X L, et al. 金元四大家论治结肠癌浅谈 [J]. Nei Mongol Journal of Traditional Chinese Medicine, 2012, 31 (7): 105 (in Chinese).

    [5] JIANG B, DING Y J. Discussion of cause and pathogenesis about rectal cancer in classical traditional Chinese medicine books [J]. Journal of Liaoning University of Traditional Chinese Medicine, 2009, 11 (4): 5 (in Chinese).

    [6] ZHU J, SHANG G B, SUN H J, et al. 结肠癌的中医病机分析及复方治疗探索 [J]. Jiangxi Journal of Traditional Chinese Medicine, 2018, 49 (12): 75 (in Chinese).

    [7] LING H, ZHANG F M, CHENG Z, et al. 黄芩等中药及其复方抗肿瘤作用研究 [J]. Acta Chinese Medicine and Pharmacology, 1998, 26 (2): 48 (in Chinese).

    [8] XU B, LIANG X F, LU J, et al. Effect of Xiao Chaihutang and its cold and hot herb-subtracted formulae on human colon carcinoma cell proliferation, lipid accumulation and alkaline phosphatase [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2018, (14): 134 (in Chinese).

    [9] CHI H G, ZHANG S H, YU F Y, et al. Effect of Huangqin Tang on Notch/Wnt pathway in mice with colitis-associated colon cancer [J]. Journal of Guangdong Medical University, 2018, 36 (4): 375 (in Chinese).

    [10] ZHANG S Q. Influence of Huangqin-Tang to proliferation of gastric cancer stem cells in vitro [D]. Fuzhou: Fujian University of Traditional Chinese Medicine, 2014 (in Chinese).

    [11] DIPAOLA R S, ZHANG H, LAMBERT G H, et al. Clinical and biologic activity of an estrogenic herbal combination (PC-SPES) in prostate cancer [J]. N Engl J Med, 1998, 339 (12): 785.

    [12] WANG S J, ZHAO J K, REN S, et al. Wogonin affects proliferation and the energy metabolism of SGC-7901 and A549 cells [J]. Exp Ther Med, 2019, 17 (1): 911.

    [13] LU H, GAO F, SHU G, et al. Wogonin inhibits the proliferation of myelodysplastic syndrome cells through the induction of cell cycle arrest and apoptosis [J]. Mol Med Rep, 2015, 12 (5): 7285.

    [14] KHALMURATOVA R, LEE M, MO J H, et al. Wogonin attenuates nasal polyp formation by inducing eosinophil apoptosis through HIF-1α and survivin suppression [J]. Sci Rep, 2018, 8 (1): 6201.

    [15] LIU X, TIAN S, LIU M, et al. Wogonin inhibits the proliferation and invasion, and induces the apoptosis of HepG2 and Bel7402 HCC cells through NF-κB/Bcl-2, EGFR and EGFR downstream ERK/AKT signaling [J]. Int J Mol Med, 2016, 38 (4): 1250.

    [16] LI S, SUN S, GAO J, et al. Wogonin induces beclin-1/PI3K and reactive oxygen species-mediated autophagy in human pancreatic cancer cells [J]. Onco Lett, 2016, 12 (6): 5059.

    [17] HUANG K F, ZHUANG Y, HUANG Y Q, et al. Experimental study on inhibitory effect of wogonin on proliferation and invasion of breast cancer cells [J]. China Journal of Chinese Materia Medica, 2014, 39 (8): 1485 (in Chinese).

    [18] SU F, ZHAO D, ZHUANG Y F, et al. Effect of wogonin on the viability, migration and invasion of hepatoma cell line SMMC-7721 [J]. Journal of Chinese Practical Diagnosis and Therapy, 2017, 31 (8): 735 (in Chinese).

    [19] WU C W, LU L, LIANG S W, et al. Application of drug-target prediction technology in network pharmacology of traditional Chinese medicine [J]. China Journal of Chinese Materia Medica, 2016, 41 (3): 377 (in Chinese).

    [20] LI X J. Network pharmacology and traditional Chinese medicine research [J]. Acta Pharmaceutica Sinica, 2018, 53 (9): 1385 (in Chinese).

    [21] WANG P, TANG S H, SU J, et al. Modern research progress of traditional Chinese medicine based on integrative pharmacology [J]. China Journal of Chinese Materia Medica, 2018, 43 (7): 12972 (in Chinese).

    [22] FAN W T, WANG Q. Mechanism of Acori Tatarinowii Rhizoma-Curcumae Radix treating depression based on network pharmacology [J]. China Journal of Chinese Materia Medica, 2018, 43 (12): 2607 (in Chinese).

    [23] RU J, LI P, WANG J, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines [J]. J Cheminform, 2014, 6 (1): 13.

    [24] The UniProt Consortium. UniProt: a worldwide hub of protein knowledge [J]. Nucleic Acids Res, 2019, doi: 10.1093/nar-lgky1049.

    [25] DENNIS G Jr, SHERMAN B T, HOSACK D A, et al. DAVID: database for annotation, visualization, and integrated discovery [J]. Genome Biol, 2003, 4 (5): P3.

    [26] KIM S J, KIM H J, KIM H R, et al. Antitumor actions of baicalein and wogonin in HT-29 human colorectal cancer cells [J]. Mol Med Rep, 2012, 6 (6): 1443.

    [27] FAN S J, CHEN Z C, ZHOU J M. 汉黄芩素对结肠癌LoVo细胞增殖、凋亡和周期及G1/S关卡调控因子的影响 [J]. Lishizhen Medicine and Materia Medica Research, 2017, 28 (3): 55 (in Chinese).

    [28] HLUBEK F, BRABLETZ T, BUDCZIES J, et al. Heterogeneous expression of Wnt/beta-catenin target genes within colorectal cancer [J]. Int J Cancer, 2010, 121 (9): 1941.

    [29] RAHMANI F, AVAN A, HASHEMY S I, et al. Role of Wnt/β-catenin signaling regulatory microRNAs in the pathogenesis of colorectal cancer [J]. J Cell Physiol, 2018, 233 (2): 811.

    [30] FODDE R, BRABLETZ T. Wnt/β-catenin signaling in cancer stemness and malignant behavior [J]. Curr Opin Cell Biol, 2007, 19 (2): 150.

    [31] CLEVERS H, NUSSE R. Wnt/β-catenin signaling and disease [J]. Cell, 2012, 149 (6): 1192.

    [32] HUANG H, HE X. Wnt/β-catenin signaling: new (and old) players and new insights [J]. Curr Opin Cell Biol, 2008, 20 (2): 119.

    [33] MI W, LIU J H, GUO M Z, et al. Peanut Skin Procyanidins reduce the expression of survivin and induce the apoptosis of pancreatic cancer cells through Wnt/beta-catenin signaling pathway [J]. Journal of Binzhou Medical University, 2017, 40 (4): 276 (in Chinese).

This Article


CN: 11-2272/R

Vol 45, No. 08, Pages 1772-1778

April 2020


Article Outline



  • 1 Materials
  • 2 Methods
  • 3 Results
  • 4 Discussion
  • References