Effect of chelerythrine on migration, invasion, and epithelial-mesenchymal transition of human ovarian cancer SKOV3 cells

Jia ZHOU,Zhidong QIU,Zhe LIN,Guangfu LYU,Jiaming XU,He LIN,Kexin WANG,Yuchen WANG,Xiaowei HUANG

PDF(1243 KB)
PDF(1243 KB)
J Jilin Univ Med Ed ›› 2024, Vol. 50 ›› Issue (1) : 25-32. DOI: 10.13481/j.1671-587X.20240104
Research in basic medicine

Effect of chelerythrine on migration, invasion, and epithelial-mesenchymal transition of human ovarian cancer SKOV3 cells

  • Jia ZHOU1,Zhidong QIU1,Zhe LIN1,Guangfu LYU2,Jiaming XU1,He LIN1,Kexin WANG1,Yuchen WANG1(),Xiaowei HUANG1,3()
Author information +
History +

Abstract

Objective To discuss the inhibitory effect of chelerythrine (CHE) on the migration, invasion, and epithelial-mesenchymal transition (EMT) of the human ovarian cancer SKOV3 cells,and to clarify the associated mechanism. Methods The SKOV3 cells were cultured in vitro and divided into control group and 2.5, 5.0, 10.0, 20.0, and 40.0 μmol·L-1 CHE groups.Methylthiazolydiphenyl-tetrazolium(MTT) assay was used to detect the inhibitory rates of proliferation of the cells in various groups. The SKOV3 cells were cultured in vitro and divided into control group, transforming growth factor-β1 (TGF-β1) group, TGF-β1+5 μmol·L-1 CHE group, and TGF-β1+10 μmol·L-1 CHE group.Cell scratch assay was used to detect the migration rates of the cells in various groups; Transwell chamber assay was used to detect the numbers of migration and invasion cells in various groups; Western blotting method was used to detect the expression levels of E-cadherin, N-cadherin, and Vimentin proteins in the cells in various groups; immunofluorescence staining method was used to detect the fluorescence intensities of E-cadherin and N-cadherin in the cells in various groups. Results The MTT assay results showed that compared with control group, the inhibitory rates of proliferation of the cells in 5.0, 10.0, 20.0, and 40.0 μmol·L-1 CHE groups were significantly increased (P<0.05 or P<0.01). The cell scratch assay results showed that compared with control group, the migration rate of the cells in TGF-β1 group was increased (P<0.01); compared with TGF-β1 group, the migration rates of the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly decreased (P<0.01). The Transwell chamber assay results showed that compared with control group, the numbers of migration and invasion cells in TGF-β1 group were significantly increased (P<0.05); compared with TGF-β1 group, the numbers of migration and invasion cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly decreased (P<0.01). The Western blotting results showed that compared with control group, the expression level of E-cadherin protein in the cells in TGF-β1 group was significantly decreased (P<0.01), while the expression levels of N-cadherin and Vimentin proteins were increased (P<0.05 or P<0.01); compared with TGF-β1 group, the expression levels of E-cadherin protein in the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased (P<0.01), and the expression levels of N-cadherin and Vimentin proteins were significantly decreased (P<0.01). The immunofluorescence staining results showed that compared with control group, the fluorescence intensity of E-cadherin in the cells in TGF-β1 group was decreased, and the fluorescence intensity of N-cadherin was increased; compared with TGF-β1 group, the fluorescence intensities of E-cadherin in the cells in TGF-β1+5 μmol·L-1 CHE group and TGF-β1+10 μmol·L-1 CHE group were significantly increased, and the fluorescence intensities of N-cadherin were decreased. Conclusion CHE can inhibit the proliferation, migration, invasion, and EMT of the human ovarian cancer SKOV3 cells.

Key words

Chelerythrine / Ovarian neoplasm / Epithelial-mesenchymal transition / Transforming growth factor-β1 / Cell migration / Cell invasion

CLC number

R285.5

Cite this article

Download Citations
Jia ZHOU,Zhidong QIU,Zhe LIN,Guangfu LYU,Jiaming XU,He LIN,Kexin WANG,Yuchen WANG,Xiaowei HUANG. Effect of chelerythrine on migration, invasion, and epithelial-mesenchymal transition of human ovarian cancer SKOV3 cells. Journal of Jilin University(Medicine Edition). 2024, 50(1): 25-32 https://doi.org/10.13481/j.1671-587X.20240104

References

1 王 稳, 王兴国, 刘淑娟, 等. 交界性卵巢肿瘤诊治中国专家共识(2022年版)[J]. 中国实用妇科与产科杂志, 2022, 38(12): 1185-1194.
2 贾艳艳. PDLIM4在卵巢癌中的临床意义及其调控肿瘤生长和转移的机制研究[D].郑州:郑州大学,2020.
3 DHALIWAL D, SHEPHERD T G. Molecular and cellular mechanisms controlling integrin-mediated cell adhesion and tumor progression in ovarian cancer metastasis: a review[J]. Clin Exp Metastasis, 2022, 39(2): 291-301.
4 VALIPOUR M, ZARGHI A, EBRAHIMZADEH M A,et al. Therapeutic potential of chelerythrine as a multi-purpose adjuvant for the treatment of COVID-19[J]. Cell Cycle, 2021, 20(22): 2321-2336.
5 LIN Y L, ZHANG Q Z, XIE B F, et al. Chelerythrine-induced apoptotic cell death in HepG2 cells involves the inhibition of Akt pathway and the activation of oxidative stress and mitochondrial apoptotic pathway[J]. Antioxidants, 2022, 11(9): 1837.
6 GONG Y, YIN S L, SUN S J, et al. Chelerythrine reverses the drug resistance of resistant Candida albicans and the biofilm to fluconazole[J]. Future Microbiol, 2022, 17: 1325-1333.
7 QIAN W D, HUANG J, ZHANG J N, et al. Antimicrobial and antibiofilm activities and mechanism of action of chelerythrine against carbapenem-resistant Serratia marcescens in vitro [J]. Microb Drug Resist, 2021, 27(8): 1105-1116.
8 CHO O, LEE J W, KIM H S, et al. Chelerythrine, a novel small molecule targeting IL-2, inhibits melanoma progression by blocking the interaction between IL-2 and its receptor[J]. Life Sci, 2023, 320: 121559.
9 WANG M Z, MA B, NI Y F, et al. Restoration of the antibiotic susceptibility of methicillin-resistant Staphylococcus aureus and extended-spectrum β-lactamases Escherichia coli through combination with chelerythrine[J].Microb Drug Resist,2021,27(3):337-341.
10 贾茗博, 孙 莹, 王 莹, 等. 氯化两面针碱通过JAK2/STAT3信号通路对胶质瘤细胞上皮-间质转化的抑制作用[J]. 吉林大学学报(医学版), 2021, 47(1): 73-81.
11 王培卿, 尹震花, 康文艺. 白屈菜红碱药理活性研究进展[J]. 中国中药杂志, 2013, 38(17): 2745-2749.
12 YANG T F, XU R, SU Q, et al. Chelerythrine hydrochloride inhibits proliferation and induces mitochondrial apoptosis in cervical cancer cells via PI3K/BAD signaling pathway[J]. Toxicol In Vitro, 2020, 68: 104965.
13 WANG J H, SONG Y J, ZHANG N, et al. Using liposomes to alleviate the toxicity of chelerythrine, a natural PKC inhibitor, in treating non-small cell lung cancer[J]. Front Oncol, 2021, 11: 658543.
14 CAO L L, LIANG Y B, ZHAO F J, et al. Chelerythrine and Fe3O4 loaded multi-walled carbon nanotubes for targeted cancer therapy[J]. J Biomed Nanotechnol, 2016, 12(6): 1312-1322.
15 CHEN Z X, YANG H, ZHANG Q L, et al. Chelerythrine inhibits stemness of cancer stem-like cells of osteosarcoma and PI3K/AKT/mTOR signal[J]. J Oncol, 2022, 2022: 6435431.
16 CHEN N Z, QI Y L, MA X, et al. Rediscovery of traditional plant medicine: an underestimated anticancer drug of chelerythrine[J]. Front Pharmacol, 2022, 13: 906301.
17 TANG Z H, CAO W X, WANG Z Y, et al. Induction of reactive oxygen species-stimulated distinctive autophagy by chelerythrine in non-small cell lung cancer cells[J]. Redox Biol, 2017, 12: 367-376.
18 PLAZAS E, AVILA M M C, MU?OZ D R, et al. Natural isoquinoline alkaloids: Pharmacological features and multi-target potential for complex diseases[J]. Pharmacol Res, 2022, 177: 106126.
19 DOHERTY J A, PERES L C, WANG C, et al. Challenges and opportunities in studying the epidemiology of ovarian cancer subtypes[J]. Curr Epidemiol Rep, 2017, 4(3): 211-220.
20 MELAMED A, RAUH-HAIN J A, GOCKLEY A A, et al. Association between overall survival and the tendency for cancer programs to administer neoadjuvant chemotherapy for patients with advanced ovarian cancer[J]. JAMA Oncol, 2021, 7(12): 1782-1790.
21 陈立兰, 狄 文. 柠檬酸合成酶对卵巢癌SKOV3细胞上皮间质转化的影响[J].现代肿瘤医学,2022,30(17): 3065-3068.
22 HUANG Y, LI C Q, ZHANG X, et al. Nanotechnology-integrated ovarian cancer metastasis therapy: insights from the metastatic mechanisms into administration routes and therapy strategies[J]. Int J Pharm, 2023, 636: 122827.
23 YOUSEFI M, DEHGHANI S, NOSRATI R,et al. Current insights into the metastasis of epithelial ovarian cancer - hopes and hurdles[J]. Cell Oncol,2020,43(4):515-538.
24 YEUNG T L, LEUNG C S, YIP K P, et al. Cellular and molecular processes in ovarian cancer metastasis. A Review in the Theme: cell and Molecular Processes in Cancer Metastasis[J]. Am J Physiol Cell Physiol, 2015, 309(7): C444-C456.
25 ANTONY J, THIERY J P, HUANG R Y. Epithelial-to-mesenchymal transition: lessons from development, insights into cancer and the potential of EMT-subtype based therapeutic intervention[J].Phys Biol,2019,16(4): 041004.
26 ASHRAFIZADEH M, MIRZAEI S, HASHEMI F,et al.New insight towards development of paclitaxel and docetaxel resistance in cancer cells: EMT as a novel molecular mechanism and therapeutic possibilities[J]. Biomedecine Pharmacother, 2021, 141: 111824.
27 白丽娜,刘 颖,唐春晓,等.可利霉素对胰腺癌细胞生物学功能的影响[J].临床肝胆病杂志, 2022,38(12): 2793-2801.
28 李 峣, 孙 莹, 宋燕珂, 等. PDGF-D通过Notch1信号通路对肿瘤细胞上皮-间质转化调控作用的研究进展[J].吉林大学学报(医学版),2022,48(1):265-270.
29 PAL M, BHATTACHARYA S, KALYAN G, et al. Cadherin profiling for therapeutic interventions in epithelial mesenchymal transition (EMT) and tumorigenesis[J]. Exp Cell Res,2018,368(2): 137-146.
30 GALVáN J A, ZLOBEC I, WARTENBERG M, et al. Expression of E-cadherin repressors SNAIL, ZEB1 and ZEB2 by tumour and stromal cells influences tumour-budding phenotype and suggests heterogeneity of stromal cells in pancreatic cancer[J].Br J Cancer,2015,112(12): 1944-1950.

Comments

PDF(1243 KB)

Accesses

Citation

Detail

Sections
Recommended

/