小鼠脂肪间质干细胞源胞外囊泡激活蛋白激酶B促进卵巢癌细胞增殖迁移和上皮间质转化

Abstract
Figure/Table
References (0)
Related Citation (15)

Download: PDF (29531 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: To explore the effect of extracellular vesicles (EVs) derived from mouse adipose-derived mesenchymal stem cells(ADSCs) on the biological behaviors of ovarian cancer ID8 cell line and its possible mechanism. Methods: ADSCs were isolated by enzyme digestion method, and identified by morphological characteristics, osteogenic and adipogenic multidirectional differentiation ability and flow cytometry surface marker detection; EVs were isolated and purified from supernatant of ADSCs by ultracentrifugation, and ADSC-EVs were identified by transmission electron microscopy, nanoparticle size analysis and Western blotting; ID8 cells were treated with ADSC-EVs at different concentrations (20 μg/mL and 40 μg/mL) and PBS as the control group. The effect of ADSC-EVs on the proliferation of ID8 cells was detected by plate cloning assay. Wound healing and Transwell test were used to detect the effect of ADSC-EVs on the migration ability of ID8 cells. The expression of epithelial-mesenchymal transition(EMT) and protein kinase B(AKT) related proteins in ID8 cells were detected by Western blotting. Results: The isolated ADSCs had typical stem cell morphology, could differentiate into osteogenesis and adipogenesis, and consistent with the general characteristics of the stem cell surface. ADSC-EVs expressed CD9 and CD81 proteins. Compared with the PBS group, the proliferation and migration of ID8 cells in ADSC-EVs group were significantly enhanced (P<0.05), and the proliferation and migration of ID8 cells in 40 μg/mL ADSC-EVS group was stronger than that in 20 μg/mL ADSCEVS group (P<0.05). With the increase of ADSC-EVS concentration, the expression of E-cadherin in ID8 cells was significantly decreased, while the expression of N-cadherin, vimentin and pAkt was greatly increased (P<0.05). Conclusion: ADSC-EVs may promote the EMT of ID8 cells by activating the phosphorylation of AKT signal, thereby enhancing their proliferation and migration ability.

Received: 12 April 2021

	Service

	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	SHEN Nahui1
	2
	SUN Xiaochun1

Cite this article:

SHEN Nahui1,2,SUN Xiaochun1.

ADSC-EVs activate protein kinase B to promote the proliferation and migration and epithelialmesenchymal transition of ovarian cancer cells

[J]. Journal of Jiangsu University(Medicine Edition), 2022, 22(1): 38-43,49.

URL:

http://zzs.ujs.edu.cn/xbyxb/EN/ OR http://zzs.ujs.edu.cn/xbyxb/EN/Y2022/V22/I1/38

［1］Chandra A, Pius C, Nabeel M, et al. Ovarian cancer: current status and strategies for improving therapeutic outcomes ［J］. Cancer Med, 2019, 8(16): 7018-7031.

［2］Katopodis P, Chudasama D, Wander G, et al. Kinase inhibitors and ovarian cancer ［J］. Cancers (Basel), 2019, 11(9): 1357.

［3］Richardson DL. New and novel therapies for gynecologic cancers ［J］. Semin Oncol Nurs, 2019, 35(2): 217-219.

［4］RomaRodrigues C, Mendes R, Baptista PV, et al. Targeting tumor microenvironment for cancer therapy［J］. Int J Mol Sci, 2019, 20(4): 840.

［5］Wu S, Zheng Q, Xing X, et al. Matrix stiffnessupregulated LOXL2 promotes fibronectin production, MMP9 and CXCL12 expression and BMDCs recruitment to assist premetastatic niche formation ［J］. J Exp Clin Cancer Res, 2018, 37(1): 99.

［6］张鑫,江梦颖,张欣怡,等.外泌体与乳腺癌耐药的研究进展［J］.临床医学,2020,40(8):118-122.

［7］Giraldo NA, SanchezSalas R, Peske JD, et al. The clinical role of the TME in solid cancer［J］. Br J Cancer, 2019, 120(1): 45-53.

［8］Rani S, Ryan AE, Griffin MD, et al. Mesenchymal stem cellderived extracellular vesicles: toward cellfree therapeutic applications［J］. Mol Ther, 2015, 23(5): 812-823.

［9］Ko SF, Yip HK, Zhen YY, et al. Adiposederived mesenchymal stem cell exosomes suppress hepatocellular carcinoma growth in a rat model: apparent diffusion coefficient, natural killer Tcell responses, and histopathological features ［J］. Stem Cells Int, 2015, 2015: 853506.

［10］朱伟,张慧,黄蓓,等.间质干细胞和肿瘤［J］.江苏大学学报（医学版）,2006,16(3):265-267.

［11］Lu JH, Wei HJ, Peng BY, et al. Adiposederived stem cells enhance cancer stem cell property and tumor formation capacity in lewis lung carcinoma cells through an interleukin6 paracrine circuit ［J］. Stem Cells Dev, 2016, 25(23): 1833-1842.

［12］Kahlert C, Kalluri R. Exosomes in tumor microenvironment influence cancer progression and metastasis ［J］. J Mol Med (Berl), 2013, 91(4): 431-437.

［13］Takebe N, Miele L, Harris PJ, et al. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update ［J］. Nat Rev Clin Oncol, 2015, 12(8): 445-464.

［14］Zhu W, Huang L, Li Y, et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo［J］. Cancer Lett, 2012, 315(1): 28-37.

［15］Zhou X, Li T, Chen Y, et al. Mesenchymal stem cellderived extracellular vesicles promote the in vitro proliferation and migration of breast cancer cells through the activation of the ERK pathway ［J］. Int J Oncol, 2019, 54(5): 1843-1852.

［16］Tang YT, Huang YY, Li JH, et al. Alterations in exosomal miRNA profile upon epithelialmesenchymal transition in human lung cancer cell lines ［J］. BMC Genomics, 2018, 19(1): 802.

［17］Liang X. EMT: new signals from the invasive front ［J］. Oral Oncol, 2011, 47(8): 686-687.

［18］Wang J, Ren D, Sun Y, et al. Inhibition of PLK4 might enhance the antitumour effect of bortezomib on glioblastoma via PTEN/PI3K/AKT/mTOR signalling pathway ［J］. J Cell Mol Med, 2020, 24(7): 3931-3947.

［19］Sun K, Luo J, Guo J, et al. The PI3K/AKT/mTOR signaling pathway in osteoarthritis: a narrative review ［J］. Osteoarthritis Cartilage, 2020, 28(4): 400-409.

［20］Wang L, Bo X, Yi X, et al. Exosometransferred LINC01559 promotes the progression of gastric cancer via PI3K/AKT signaling pathway ［J］. Cell Death Dis, 2020, 11(9): 723.

［21］Gu H, Ji R, Zhang X, et al. Exosomes derived from human mesenchymal stem cells promote gastric cancer cell growth and migration via the activation of the Akt pathway ［J］. Mol Med Rep, 2016, 14(4): 3452-3458.