Vol 7, No 4 (2022)
Original article
Published online: 2022-11-29

open access

Page views 3447
Article views/downloads 350
Get Citation

Connect on Social Media

Connect on Social Media

Synergistic effect of oxymatrine and 5-fluorouracil on the migratory potential in A549 non-small cell lung cancer cells

Agnieszka Mlicka1, Wioletta Zielińska2, Klaudia Mikołajczyk2, Marta Hałas-Wiśniewska2, Magdalena Izdebska12, Alina Grzanka2
Medical Research Journal 2022;7(4):293-300.


Introduction: An interesting research direction is the development of new therapies to reduce metastasis, especially in highly invasive cancer such as lung cancer. One of the commonly used anti-cancer drugs is 5-fluorouracil. Oxymatrine is a natural alkaloid with a wide range of effects. Combined with a cytostatic, it may enhance its action and protect normal cells. Therefore, the study aimed to analyse the effect of oxymatrine and 5-fluorouracil on non-small lung cancer cell line A549.

Material and methods: The study was based on the assessment of the interaction between drugs, cell death, cell cycle phase distribution, fluorescent labelling of F-actin and b-catenin, as well as wound healing and transwell migration assay.

Results: The combined treatment with oxymatrine and the cytostatic in a 1:1 ratio resulted in synergism. Incubation of cells with both substances induced changes in the life processes of A549 cells. In turn, the reorganization of F-actin and b-catenin contributed to the limitation of lung cancer cell migration compared to individual treatment with compounds.

Conclusions: This study demonstrated that the combination of oxymatrine and 5-fluorouracil in the 1:1 ratio may limit the migratory potential of A549 cells. In summary, oxymatrine can support the anti-cancer effect of 5-fluorouracil, but its potential application should be examined in further studies.

Article available in PDF format

View PDF Download PDF file


  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018; 68(1): 7–30.
  2. Shao Y, Liang B, Long F, et al. Diagnostic microrna biomarker discovery for non-small-cell lung cancer adenocarcinoma by integrative bioinformatics analysis. Biomed Res Int. 2017; 2017: 2563085.
  3. Cao F, Shi M, Yu Bo, et al. Epigenetic mechanism of enrichment of A549 lung cancer stem cells with 5-fu. Onco Targets Ther. 2021; 14: 3783–3794.
  4. Chang A. Chemotherapy, chemoresistance and the changing treatment landscape for NSCLC. Lung Cancer. 2011; 71(1): 3–10.
  5. Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003; 3(5): 330–338.
  6. Zhao JG, Ren KM, Tang J. Overcoming 5-Fu resistance in human non-small cell lung cancer cells by the combination of 5-Fu and cisplatin through the inhibition of glucose metabolism. Tumour Biol. 2014; 35(12): 12305–12315.
  7. Aghamiri S, Jafarpour A, Zandsalimi F, et al. Effect of resveratrol on the radiosensitivity of 5-FU in human breast cancer MCF-7 cells. J Cell Biochem. 2019; 120(9): 15671–15677.
  8. Halim CE, Xinjing SL, Fan Lu, et al. Anti-cancer effects of oxymatrine are mediated through multiple molecular mechanism(s) in tumor models. Pharmacol Res. 2019; 147: 104327.
  9. Xiao Xu, Hou X, Shi W, et al. Oxymatrine inhibits proliferation and apoptosis of human breast cancer cells through the regulation of miRNA-140-5P. Am J Transl Res. 2021; 13(12): 13674–13682.
  10. Li X, Sun J, Xu Q, et al. Oxymatrine inhibits colorectal cancer metastasis via attenuating pkm2-mediated aerobic glycolysis. Cancer Manag Res. 2020; 12: 9503–9513.
  11. Wu C, Huang W, Guo Y, et al. Oxymatrine inhibits the proliferation of prostate cancer cells in vitro and in vivo. Mol Med Rep. 2015; 11(6): 4129–4134.
  12. Yu Q, Luo J, Zhang J, et al. Oxymatrine inhibits the development of non-small cell lung cancer through miR-367-3p upregulation and target gene downregulation. Am J Transl Res. 2020; 12(9): 5538–5550.
  13. Pan Di, Zhang W, Zhang N, et al. Oxymatrine synergistically enhances doxorubicin anticancer effects in colorectal cancer. Front Pharmacol. 2021; 12: 673432.
  14. Zhang YY, Yi M, Huang YP. Oxymatrine ameliorates doxorubicin-induced cardiotoxicity in rats. Cell Physiol Biochem. 2017; 43(2): 626–635.
  15. Jung H, Wang SY, Yang IW, et al. Detection and treatment of mycoplasma contamination in cultured cells. Chang Gung Med J. 2003; 26(4): 250–258.
  16. Chou TC. Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev. 2006; 58(3): 621–681.
  17. Izdebska M, Gagat M, Grzanka A. Overexpression of lamin B1 induces mitotic catastrophe in colon cancer LoVo cells and is associated with worse clinical outcomes. Int J Oncol. 2018; 52(1): 89–102.
  18. Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71(3): 209–249.
  19. Jin Y, Liu J, Liu Y, et al. Oxymatrine inhibits renal cell carcinoma progression by suppressing β-catenin expression. Front Pharmacol. 2020; 11: 808.
  20. Li W, Yu X, Tan S, et al. Oxymatrine inhibits non-small cell lung cancer via suppression of EGFR signaling pathway. Cancer Med. 2018; 7(1): 208–218.
  21. Lee Ck, Jung M, Jung I, et al. Cumulative metformin use and its impact on survival in gastric cancer patients after gastrectomy. Ann Surg. 2016; 263(1): 96–102.
  22. Khakbaz P, Panahizadeh R, Vatankhah MA, et al. Allicin reduces 5-fluorouracil-resistance in gastric cancer cells through modulating MDR1, DKK1, and WNT5A expression. Drug Res (Stuttg). 2021; 71(8): 448–454.
  23. He WT, Zhu YH, Zhang T, et al. Curcumin reverses 5-fluorouracil resistance by promoting human colon cancer HCT-8/5-FU cell apoptosis and down-regulating heat shock protein 27 and p-glycoprotein. Chin J Integr Med. 2019; 25(6): 416–424.
  24. Fan YX, Abulimiti P, Zhang HL, et al. Mechanism of reversal of multidrug resistance by curcumin in human colorectal cancer cell line HCT-8/5-FU. Genet Mol Res. 2017; 16(2).
  25. Ye J, Zou MM, Li P, et al. Oxymatrine and cisplatin synergistically enhance anti-tumor immunity of CD8 T cells in non-small cell lung cancer. Front Oncol. 2018; 8: 631.
  26. Liang Li, Wu J, Luo J, et al. Oxymatrine reverses 5-fluorouracil resistance by inhibition of colon cancer cell epithelial-mesenchymal transition and NF-κB signaling . Oncol Lett. 2020; 19(1): 519–526.
  27. Wigmore PM, Mustafa S, El-Beltagy M, et al. Effects of 5-FU. Adv Exp Med Biol. 2010; 678: 157–164.
  28. VanderVeen BN, Sougiannis AT, Velazquez KT, et al. The acute effects of 5 fluorouracil on skeletal muscle resident and infiltrating immune cells in mice. Front Physiol. 2020; 11: 593468.
  29. Zielińska W, Nawrocka A, Rydzkowski M, et al. Possibilities in the application of solid lipid nanoparticles in combination with 5-fluorouracil to overcome the drugresistance of non-small cell lung cancer cell line A549. Medical Research Journal. 2020; 5(1): 1–8.
  30. Li J, Jiang K, Zhao F. Oxymatrine suppresses proliferation and facilitates apoptosis of human ovarian cancer cells through upregulating microRNA‑29b and downregulating matrix metalloproteinase‑2 expression. Mol Med Rep. 2015; 12(4): 5369–5374.
  31. Liu F, Wang B, Wang J, et al. Oxymatrine inhibits proliferation and migration while inducing apoptosis in human glioblastoma cells. Biomed Res Int. 2016; 2016: 1784161.