Volume 22 Issue 6
Jun.  2024
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GAO Jie, LI Jiangyan, HUANG Hua, ZHANG Lunjun, DENG Rong. Effects of exosomes derived from hepatocellular carcinoma cells on their biological behaviors of proliferation, apoptosis and autophagy[J]. Chinese Journal of General Practice, 2024, 22(6): 936-939. doi: 10.16766/j.cnki.issn.1674-4152.003538
Citation: GAO Jie, LI Jiangyan, HUANG Hua, ZHANG Lunjun, DENG Rong. Effects of exosomes derived from hepatocellular carcinoma cells on their biological behaviors of proliferation, apoptosis and autophagy[J]. Chinese Journal of General Practice, 2024, 22(6): 936-939. doi: 10.16766/j.cnki.issn.1674-4152.003538

Effects of exosomes derived from hepatocellular carcinoma cells on their biological behaviors of proliferation, apoptosis and autophagy

doi: 10.16766/j.cnki.issn.1674-4152.003538
Funds:

 82200661

 2020byzd059

 2020byzd029

  • Received Date: 2024-03-04
    Available Online: 2024-07-22
  •   Objective  Exosomes play an important role in the occurrence and development of hepatocellular carcinoma. This study aims to investigate the effects of exosomes on the proliferation, apoptosis, autophagy, and exosome release of HepG2 hepatocellular carcinoma cells and the related mechanisms.  Methods  Exosomes of HepG2 cells were extracted by ultrafast centrifugation. Exosome morphology, diameter distribution and marker protein expression of HepG2 cells were analyzed by transmission electron microscopy, nanoparticle tracking and Western blotting analysis. After the co-culture of exosomes and HepG2 cells, a CCK-8 kit was used to detect the proliferation of HepG2 cells, the apoptosis of HepG2 cells was detected by flow cytometry, and the expressions of apoptosis-related proteins (Bax, Bcl-2) and autophagy-related proteins (LC3-Ⅱ/LC3-Ⅰ, p62, Beclin-1) were detected by Western blotting.  Results  The morphology of exosomes extracted from HepG2 cells was consistent with the characteristics of exosomes, and the diameter between 30 and 150 nm. The marker proteins Alix and CD63 were significantly expressed. The results of CCK-8 showed that the absorbance of HepG2 cells in the 24 h exosome group was not significantly different from that in the control group(P > 0.05), but the absorbance of the exosome group at 48 hours and 72 hours were higher than that of the control group (P < 0.05). Flow cytometry showed that the apoptosis rate was (14.96±0.28) % in the control group and (11.16±0.50) % in the exosome group, and the apoptosis rate decreased (t=11.485, P < 0.001). Western blotting results showed that compared with the control group, the expression of apoptosis-related protein Bcl-2 in exosome group was up-regulated (P < 0.01), and the expression of Bax was down-regulated (P < 0.01). Autophagy associated protein LC3-Ⅱ/LC3-Ⅰ expression was up-regulated (P < 0.01), Beclin-1 expression was up-regulated (P < 0.05), and p62 expression was down-regulated (P < 0.01).  Conclusion  Exosomes derived from HepG2 cells can promote cell proliferation and inhibit apoptosis by inducing up-regulation of autophagy.

     

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  • [1]
    SUNG H, FERLAY J, SIEGEL R L, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
    [2]
    CHEN R, XU X, TAO Y Q, et al. Exosomes in hepatocellular carcinoma: a new horizon[J]. Cell Commun Signal, 2019, 17(1): 1. doi: 10.1186/s12964-018-0315-1
    [3]
    ZELLI V, COMPAGNONI C, CAPELLI R, et al. Role of exosomal microRNAs in cancer therapy and drug resistance mechanisms: focus on hepatocellular carcinoma[J]. Front Oncol, 2022, 12: 940056. DOI: 10.3389/fonc.2022.940056.
    [4]
    SU Y Y, CHAO C H, HSU H Y, et al. DDX3 suppresses hepatocellular carcinoma progression through modulating the secretion and composition of exosome[J]. Am J Cancer Res, 2023, 13(5): 1744-1765.
    [5]
    XI L, PENG M X, LIU S Q, et al. Hypoxia-stimulated ATM activation regulates autophagy-associated exosome release from cancer-associated fibroblasts to promote cancer cell invasion[J]. J Extracell Vesicles, 2021, 10(11): e12146. DOI: 10.1002/jev2.12146.
    [6]
    XIE Q H, ZHENG J Q, DING J Y, et al. Exosome-mediated immunosuppression in tumor microenvironments[J]. Cells, 2022, 11(12): 1946. doi: 10.3390/cells11121946
    [7]
    BAI J F, HUANG M, SONG B H, et al. The current status and future prospects for conversion therapy in the treatment of hepatocellular carcinoma[J]. Technol Cancer Res Treat, 2023. DOI: 10.1177/15330338231159718.
    [8]
    QU Z, FENG J W, PAN H, et al. Exosomes derived from HCC cells with different invasion characteristics mediated EMT through TGF-β/Smad signaling pathway[J]. Onco Targets Ther, 2019, 12: 6897-6905. doi: 10.2147/OTT.S209413
    [9]
    LIU C J, REN C N, GUO L, et al. Exosome-mediated circTTLL5 transfer promotes hepatocellular carcinoma malignant progression through miR-136-5p/KIAA1522 axis[J]. Pathol Res Pract, 2023, 241: 154276. DOI: 10.1016/j.prp.2022.154276.
    [10]
    LI X, LI C Y, ZHANG L Q, et al. The significance of exosomes in the development and treatment of hepatocellular carcinoma[J]. Mol Cancer, 2020, 19(1): 1. doi: 10.1186/s12943-019-1085-0
    [11]
    HAN Q J, ZHAO H J, JIANG Y, et al. HCC-Derived Exosomes: critical player and target for cancer immune escape[J]. Cells, 2019, 8(6): 558. doi: 10.3390/cells8060558
    [12]
    YANG K K, ZHOU Q B, QIAO B B, et al. Exosome-derived noncoding RNAs: function, mechanism, and application in tumor angiogenesis[J]. Mol Ther Nucleic Acids, 2022, 27: 983-997. doi: 10.1016/j.omtn.2022.01.009
    [13]
    GE Y, MU W, BA Q, et al. Hepatocellular carcinoma-derived exosomes in organotropic metastasis, recurrence and early diagnosis application[J]. Cancer Lett, 2020, 477: 41-48. doi: 10.1016/j.canlet.2020.02.003
    [14]
    邹敏, 游逾, 何松, 等. 缺氧外泌体对肝癌Huh7细胞增殖、迁移及侵袭的影响[J]. 中华肝脏病杂志, 2019, 27(5): 363-368. doi: 10.3760/cma.j.issn.1007-3418.2019.05.008

    ZOU M, YOU Y, HE S, et al. Effects of hypoxic exosomes on the proliferation, migration and invasion of hepatocellular carcinoma Huh7 cells[J]. Chin J Hepatol, 2019, 27(5): 363-368. doi: 10.3760/cma.j.issn.1007-3418.2019.05.008
    [15]
    WEI X N, YANG Z H, CHEN G M, et al. VMP1 promotes exosome secretion and enhances 5-FU resistance in colon cancer cells[J]. Tissue Cell, 2022, 77: 101851. DOI: 10.1016/j.tice.2022.101851.
    [16]
    符山花, 包利利, 赵达, 等. ABT-737对M2型TAM来源外泌体处理的卵巢癌细胞SKOV3自噬性凋亡与干性特征的影响[J]. 西部医学, 2023, 35(5): 654-661, 669. doi: 10.3969/j.issn.1672-3511.2023.05.005

    FU S H, BAO L L, ZHAO D, et al. Effects of ABT-737 on autophagy apoptosis and stemness characteristics of SKOV3 ovarian cancer cells treated with M2 tumor-associated macrophage-derived exosomes[J]. Med J West China, 2023, 35(5): 654-661, 669. doi: 10.3969/j.issn.1672-3511.2023.05.005
    [17]
    YAZDANI H O, HUANG H, TSUNG A. Autophagy: dual response in the development of hepatocellular carcinoma[J]. Cells, 2019, 8(2): 91. doi: 10.3390/cells8020091
    [18]
    童里, 郑小飞, 顾旺, 等. 细胞自噬在肝细胞肝癌中的研究现状[J]. 中华全科医学, 2023, 21(4): 672-676. doi: 10.16766/j.cnki.issn.1674-4152.002957

    TONG L, ZHENG X F, GU W, et al. Research status of autophagy in hepatocellular carcinoma[J]. Chinese Journal of General Practice, 2023, 21(4): 672-676. doi: 10.16766/j.cnki.issn.1674-4152.002957
    [19]
    KOUROUMALIS E, TSOMIDIS I, VOUMVOURAKI A. Pathogenesis of hepatocellular carcinoma: the interplay of apoptosis and autophagy[J]. Biomedicines, 2023, 11(4): 1166. doi: 10.3390/biomedicines11041166
    [20]
    MA W J, ZHOU Y, LIU M, et al. Long non-cod-ing RNA LINC00470 in serum derived exosome: a critical regulator for proliferation and autophagy in glioma cells[J]. Cancer Cell Int, 2021, 21(1): 149. doi: 10.1186/s12935-021-01825-y
    [21]
    YAO W J, GUO P, MU Q M, et al. Exosome-derived circ-PVT1 contributes to cisplatin resistance by regulating autophagy, invasion, and apoptosis via miR-30a-5p/YAP1 axis in gastric cancer cells[J]. Cancer Biother Radiopharm, 2021, 36(4): 347-359.
    [22]
    LIAO M M, QIN M R, LIU L H, et al. Exosomal microRNA profiling revealed enhanced autophagy suppression and anti-tumor effects of a combination of compound Phyllanthus urinaria and lenvatinib in hepatocellular carcinoma[J]. Phytomedicine, 2024, 122: 155091. DOI: 10.1016/j.phymed.2023.155091.
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