DFOG inhibits invasion and migration of SKOV3 ovarian cancer stem-like cells in vitro via down-regulating CD44 expression

LIN Jiazhi; LIU Huiling; DENG Yu'ao; ZHANG Chen; NING Yingxia

PDF(2859 KB)

Journal of Hunan Normal University(Medical Science) ›› 2023, Vol. 20 ›› Issue (2) : 16-21.

DFOG inhibits invasion and migration of SKOV3 ovarian cancer stem-like cells in vitro via down-regulating CD44 expression

LIN Jiazhi¹, LIU Huiling¹, DENG Yu'ao², ZHANG Chen³, NING Yingxia¹

Author information +

History +

Abstract

Objective To determine whether 7-Difluoromethoxyl-5, 4'-di-n-octyl genistein (DFOG) inhibits invasion and migration capabilities in SKOV3-derived ovarian cancer stem-like cells (OCSLCs) by downregulating the expression of CD44, a cancer stem cell surface marker. Methods CD44 gene was knocked down using the lentiviral delivery system. OCSLCs cells were treated with DFOG (0.1, 1.0 and 10 μM) or in combination with DFOG (10 μM) and shCD44. The expression levels of CD44 protein in OCSLCs infected with CD44 shRNA and treated with DFOG (0.1, 1.0 and 10.0 µM) were detected using western blot analysis. The cell invasion rates were determined using transwell invasion assay and cell migration rates were determined using Wound-Healing assay. Results CD44 knockdown significantly reduced the cell invasion rates and cell migration rates in OCSLCs cells. DFOG downregulated the expression of CD44 as well as attenuated cell invasion and cell migration capabilities in OCSLCs. Moreover, knockdown of CD44 gene collaborated with DFOG to inhibit the ability of cell invasion and cell migration in OCSLCs. Conclusion DFOG inhibits cell invasion and cell migration capabilities by downregulating CD44 expression in OCSLCs .

Key words

ovarian cancer / cancer stem-like cells / DFOG / CD44 / cell invasion / cell migration

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

LIN Jiazhi, LIU Huiling, DENG Yu'ao, ZHANG Chen, NING Yingxia. DFOG inhibits invasion and migration of SKOV3 ovarian cancer stem-like cells in vitro via down-regulating CD44 expression[J]. Journal of Hunan Normal University(Medical Science). 2023, 20(2): 16-21

References

[1] Siegel RL, Miller KD, Jemal A.Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30.
[2] Vaughan S, Coward JI, Bast RC, et al.Rethinking ovarian cancer: recommendations for improving outcomes[J]. Nat Rev Cancer, 2011, 11(10): 719-725.
[3] Ayob AZ, Ramasamy TS.Cancer stem cells as key drivers of tumour progression[J]. J Biomed Sci, 2018, 25(1): 20.
[4] Kuşoğlu A, Biray Avcı Ç.Cancer stem cells: a brief review of the current status[J]. Gene, 2019, 681: 80-85.
[5] Jiang YX, Siu MKY, Wang JJ, et al.Ascites-derived ALDH+CD44+ tumour cell subsets endow stemness, metastasis and metabolic switch via PDK4-mediated STAT3/AKT/NF-κB/IL-8 signalling in ovarian cancer[J]. Br J Cancer, 2020, 123(2): 275-287.
[6] Hu L, McArthur C, Jaffe RB. Ovarian cancer stem-like side-population cells are tumourigenic and chemoresistant[J]. Br J Cancer, 2010, 102(8): 1276-1283.
[7] Abubaker K, Latifi A, Luwor R, et al.Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden[J]. Mol Cancer, 2013, 12: 24.
[8] Zhao Y, He M, Cui L, et al.Chemotherapy exacerbates ovarian cancer cell migration and cancer stem cell-like characteristics through GLI1[J]. Br J Cancer, 2020, 122(11): 1638-1648.
[9] Zhang J, Chen X, Bian L, et al.CD44+/CD24+-Expressing Cervical Cancer Cells and Radioresistant Cervical Cancer Cells Exhibit Cancer Stem Cell Characteristics[J]. Gynecol Obstet Invest, 2019, 84(2): 174-182.
[10] Zhang J, Yuan B, Zhang H, et al.Human epithelial ovarian cancer cells expressing CD105, CD44 and CD106 surface markers exhibit increased invasive capacity and drug resistance[J]. Oncol Lett, 2019, 17(6): 5351-5360.
[11] Ning Y, Luo C, Ren K, et al.FOXO3a-mediated suppression of the self-renewal capacity of sphere-forming cells derived from the ovarian cancer SKOV3 cell line by 7-difluoromethoxyl-5, 4'-di-n-octyl genistein[J]. Mol Med Rep, 2014, 9(5): 1982-1988.
[12] Li Y, Wicha MS, Schwartz SJ, et al.Implications of cancer stem cell theory for cancer chemoprevention by natural dietary compounds[J]. J Nutr Biochem, 2011, 22(9): 799-806.
[13] 吕小林, 向红琳, 曹建国, 等.7-二氟甲氧基-5, 4′-二-正辛烷氧基金雀异黄素诱导肺癌A549细胞凋亡[J]. 肿瘤药学, 2011, 1(4): 342-346.
[14] 曹晓正. 7-二氟甲氧基-5, 4′-二—正辛烷氧基异黄酮对SGC-7901胃癌干样细胞EMT和侵袭的影响[D]. 长沙: 湖南师范大学, 2015.
[15] Ning Y, Xu M, Cao X, et al.Inactivation of AKT, ERK and NF-κB by genistein derivative, 7-difluoromethoxyl-5, 4'-di-n-octylygenistein, reduces ovarian carcinoma oncogenicity[J]. Oncol Rep, 2017, 38(2): 949-958.
[16] Ning YX, Li QX, Xiang HL, et al.Apoptosis induced by 7-difluoromethoxyl-5, 4'-di-n-octyl genistein via the inactivation of FoxM1 in ovarian cancer cells[J]. Oncol Rep, 2012, 27(6): 1857-1864.
[17] 宁映霞, 曹建国.7-二氟甲氧基-5, 4'-二正辛烷氧基金雀异黄素对卵巢癌干细胞样细胞自我更新和FoxM1表达的影响[J]. 湖南师范大学学报 (医学版), 2014, 11(1): 10-13.
[18] 宁映霞, 邓宇傲, 曹建国. DFOG抑制卵巢癌A2780细胞系球形成细胞自我更新与活化FoxO3a相关[J]. 湖南师范大学学报 (医学版), 2014, 11(2): 1-4.
[19] 蒋明芳. IL-37通过IL-6/STAT3信号通路抑制NSCLC细胞侵袭和转移的机制研究[D]. 青岛: 青岛大学, 2018.
[20] Skandalis SS, Karalis TT, Chatzopoulos A, et al.Hyaluronan-CD44 axis orchestrates cancer stem cell functions[J]. Cell Signal, 2019, 63: 109377.
[21] Thapa R, Wilson GD.The Importance of CD44 as a Stem Cell Biomarker and Therapeutic Target in Cancer[J]. Stem Cells International, 2016, 2016: 2087204.
[22] Zhu J, Huang G, Hua X, et al.CD44s is a crucial ATG7 downstream regulator for stem-like property, invasion, and lung metastasis of human bladder cancer (BC) cells[J]. Oncogene, 2019, 38(17): 3301-3315.
[23] Zou W, Zhang Y, Bai G, et al.siRNA-induced CD44 knockdown suppresses the proliferation and invasion of colorectal cancer stem cells through inhibiting epithelial-mesenchymal transition[J]. J Cell Mol Med, 2022, 26(7): 1969-1978.
[24] Vahidian F, Safarzadeh E, Mohammadi A, et al.siRNA-mediated silencing of CD44 delivered by Jet Pei enhanced Doxorubicin chemo sensitivity and altered miRNA expression in human breast cancer cell line (MDA-MB468)[J]. Mol Biol Rep, 2020, 47(12): 9541-9551.
[25] 孟娅妮, 于海伦, 白军.7-二氟甲氧基-5, 4'-二正辛烷氧基金雀异黄素钝化Pim-1对宫颈癌细胞增殖和侵袭的抑制作用[J]. 中国现代应用药学, 2016, 33(8): 1010-1016.