Microvesicles mediate sorafenib resistance in liver cancer cells through attenuating p53 and enhancing FOXM1 expression

Ali, Doulathunnisa Jaffar; He, Cong; Xu, Han; Kumaravel, Subhashree; Sun, Bo; Zhou, Yunting; Liu, Rui; Zhang, Xiao

doi:10.1016/j.lfs.2021.119149

Cited by 10 publications

(10 citation statements)

References 44 publications

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“…EVs containing protein CD147 released by HCC cells activate the NF-κB pathway of surrounding fibroblasts, induce MMP-9 expression, and stimulate the ERK1/2 and p38 MAPK pathways, leading to extracellular matrix degradation and tumor invasion ( 136 , 137 ). In addition, EVs containing miR-25 released from HCC cells inhibited p53 expression in surrounding HCC cells, thereby restoring FOXM1 (a key regulator of cell cycle progression) expression, activating the HGF/Ras pathway, reversing the expression of sorafenib-induced apoptotic markers BCL2 and BAX, making HCC cells resistant to sorafenib ( 138 ). miR-34a is reduced in the large EVs released by CHB or HCC cells, resulting in increased levels of mRNA and protein in c-Mets in surrounding cells, promoting phosphorylation of c-Met-induced extracellular signal- regulated kinases 1 and 2 (ERK1/2), thereby facilitating CHB conversion to HCC ( 139 , 140 ).…”

Section: Interactions Between Hcc and Hcc Cell-derived Evsmentioning

confidence: 99%

Extracellular Vesicles and Hepatocellular Carcinoma: Opportunities and Challenges

Wang

Zhang

et al. 2022

Front. Oncol.

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The incidence of hepatocellular carcinoma (HCC) is increasing worldwide. Extracellular vesicles (EVs) contain sufficient bioactive substances and are carriers of intercellular information exchange, as well as delivery vehicles for nucleic acids, proteins and drugs. Although EVs show great potential for the treatment of HCC and their role in HCC progression has been extensively studied, there are still many challenges such as time-consuming extraction, difficult storage, easy contamination, and low drug loading rate. We focus on the biogenesis, morphological characteristics, isolation and extraction of EVs and their significance in the progression of HCC, tumor invasion, immune escape and cancer therapy for a review. EVs may be effective biomarkers for molecular diagnosis of HCC and new targets for tumor-targeted therapy.

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Section: Interactions Between Hcc and Hcc Cell-derived Evsmentioning

confidence: 99%

Extracellular Vesicles and Hepatocellular Carcinoma: Opportunities and Challenges

Wang

Zhang

et al. 2022

Front. Oncol.

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“…Interestingly, the transport of anti-cancer drugs out of ovarian cancer cells through their secreted EVs supported the role of EVs in cancer progression and treatment. Conversely, the observation of more sorafenib resistance in HCC tumors that were treated with tumor cell-derived MVs added evidence to the noticeable link between MVs and sorafenib resistance [ 15 , 78 ] .…”

Section: Mvs: the Tiny Mediators In Intercellular Communicationmentioning

confidence: 99%

“…For example, miRNAs involved in the regulation of multiple mRNA targets in recipient cells were found to be enriched in TMVs [ 94 - 97 ] . In recent years, our group also found that HCC cell-derived MVs could increase sorafenib drug resistance by inducing FOXM1 expression via miR-25 transferred to the recipient liver cancer cells from the parent cells both in vitro and in vivo [ 15 ] . Similarly, long non-coding RNA (lnc-ROR and lnc-VLDLR)-enriched HCC cells-secreted vesicles (especially after sorafenib exposure) were proved to reduce apoptosis induced by chemotherapy [ 88 , 89 ] .…”

Section: The Dynamic Impact Of Mvs On Sorafenib Resistancementioning

confidence: 99%

“…Several emerging studies reported utilizing modified EVs to overcome chemoresistance during cancer treatments. As a naturally secreted nanoparticle, MVs exhibited excellent specific tissue homing ability and acted as good functional carriers for various therapeutic molecules [ 15 , 74 , 100 ] . To achieve bioactive and continuous drug containing MVs, the pre-loading strategy has been applied to modify donor cells.…”

Section: The Dynamic Impact Of Mvs On Sorafenib Resistancementioning

confidence: 99%

“…Microvesicles (MVs), functional mediators in cell-to-cell communication by transferring bioactive cargoes [ 10 ] , play an important role in tumor progression and metastasis [ 11 - 14 ] . Interestingly, recent studies reported that HCC-derived MVs promoted sorafenib resistance in recipient liver cancer cells by transporting cancerous cargo compared to normal liver cell-derived MVs [ 15 ] . Thus, the role of these tiny functional vesicles needs to be cautiously studied for the in-depth understanding and successful treatment of HCC over sorafenib resistance.…”

Section: Introductionmentioning

confidence: 99%

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Microvesicles: the functional mediators in sorafenib resistance

Ali

Sun

et al. 2022

Cancer Drug Resist

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Overcoming drug resistance in cancer therapies remains challenging, and the tumor microenvironment plays an important part in it. Microvesicles (MVs) are functional natural carriers of cellular information, participate in intercellular communication, and dynamically regulate the tumor microenvironment. They contribute to drug resistance by transferring functional molecules between cells. Conversely, due to their specific cell or tissue targeting ability, MVs are considered as carriers for therapeutic molecules to reverse drug resistance. Thus, in this mini-review, we aim to highlight the crucial role of MVs in cell-to-cell communication and therefore their diverse impact mainly on liver cancer progression and treatment. In addition, we summarize the possible mechanisms for sorafenib resistance (one of the main hurdles in hepatocellular carcinoma treatments) and recent advances in using MVs to reverse sorafenib resistance in liver cancer therapies. Identifying the functional role of MVs in cancer therapy might provide a new aspect for developing precise novel therapeutics in the future.

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Effect of human bone marrow mesenchymal stem cell-derived microvesicles on the apoptosis of the multiple myeloma cell line U266

Vafaeizadeh,

Abroun,

Soufi Zomorrod

2024

J Cancer Res Clin Oncol

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Background Microvesicles are membraned particles produced by different types of cells recently investigated for anticancer purposes. The current study aimed to investigate the effects of human bone marrow mesenchymal stem cell-derived microvesicles (BMSC-MVs) on the multiple myeloma cell line U266. BMSC-MVs were isolated from BMSCs via ultracentrifugation and characterized using transmission electron microscopy (TEM) and dynamic light scattering (DLS). U266 cells were treated with 15, 30, 60, and 120 µg/mL BMSC-MVs for three and seven days and the effects of treatment in terms of viability, cytotoxicity, and DNA damage were investigated via the MTT assay, lactate dehydrogenase (LDH) assay, and 8‑hydroxy-2’-deoxyguanosine (8‑OHdG) measurement, respectively. Moreover, the apoptosis rate of the U266 cells treated with 60 µg/mL BMSC-MVs was also assessed seven days following treatment via flow cytometry. Ultimately, the expression level of BCL2, BAX, and CCND1 by the U266 cells was examined seven days following treatment with 60 µg/mL BMSC-MVs using qRT-PCR. Results BMSC-MVs had an average size of ~ 410 nm. According to the MTT and LDH assays, BMSC-MV treatment reduced the U266 cell viability and mediated cytotoxic effects against them, respectively. Moreover, elevated 8‑OHdG levels following BMSC-MV treatment demonstrated a dose-dependent increase of DNA damage in the treated cells. BMSC-MV-treated U266 cells also exhibited an increased apoptosis rate after seven days of treatment. The expression level of BCL2 and CCND1 decreased in the treated cells whereas the BAX expression demonstrated an incremental pattern. Conclusions Our findings accentuate the therapeutic benefit of BMSC-MVs against the multiple myeloma cell line U266 and demonstrate how microvesicles could be of therapeutic advantage. Future in vivo studies could further corroborate these findings.

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Microvesicles mediate sorafenib resistance in liver cancer cells through attenuating p53 and enhancing FOXM1 expression

Cited by 10 publications

References 44 publications

Extracellular Vesicles and Hepatocellular Carcinoma: Opportunities and Challenges

Extracellular Vesicles and Hepatocellular Carcinoma: Opportunities and Challenges

Microvesicles: the functional mediators in sorafenib resistance

Effect of human bone marrow mesenchymal stem cell-derived microvesicles on the apoptosis of the multiple myeloma cell line U266

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