Effects of ATP-binding cassette transporter G2 in extracellular vesicles on drug resistance of laryngeal cancer cells in <i>in vivo</i> and <i>in vitro</i>

Zhao, Yan; Chen, Yuetong; Wang, Jing; Liu, Liang

doi:10.3892/ol.2021.12625

Cited by 6 publications

(2 citation statements)

References 56 publications

(61 reference statements)

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“…The regulation of the cell cycle is usually dependent on G 1 phase arrest. The proliferation index (PI) is calculated using the following formula ( 45 ): PI=(S + G 2 /M)/(G 0 /G 1 + S + G 2 /M) ×100%. As shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

Compound Kushen injection attenuates angiotensin II‑mediated heart failure by inhibiting the PI3K/Akt pathway

Wang

Yang

et al. 2023

Int J Mol Med

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Compound Kushen injection (CKI) is a type of traditional Chinese medicine that has previously been studied for the treatment of various types of cancer. Previous studies have reported that CKI regulates cell apoptosis by downregulating the PI3K/Akt pathway. The present study aimed to determine whether CKI alleviates heart failure (HF) by attenuating cardiomyocyte apoptosis via the inhibition of the PI3K/Akt pathway. Angiotensin II (Ang II) was used to elicit HF, and osmotic minipumps with either Ang II (2 µg/kg/day) or phosphate-buffered saline (PBS; 200 µl) were subcutaneously implanted into 6-week-old male C57BL/6 mice for 3 weeks. In addition, PBS or CKI (25 mg/kg/day) were subcutaneously infused once a day for 3 weeks. Echocardiography was used to examine hemodynamics. The myocardial injury biomarkers, cardiac troponin I and N-terminal (NT)-pro hormone B-type natriuretic peptide, were assessed using enzyme-linked immunosorbent assay. Transmission electron microscopy was used to determine the morphology of the myocardium. The rate of apoptosis was detected using TUNEL staining and flow cytometry (FCM), and the expression levels of apoptosis-related proteins were measured using western blot (WB) analysis. Moreover, H9C2 cells were treated with CKI (2 mg/ml) or LY294002 (an inhibitor of the PI3K/Akt pathway; 25 µmol/l) in combination with Ang II (1 µmol/l) for 48 h. Cell Counting Kit-8 assay, FCM and WB analysis were performed in the H9C2 cells to examine cell viability, cell cycle distribution and representative signaling proteins. It was found that CKI promoted healthy cardiac function, reduced myocardial structural damage and reduced the rate of cardiomyocyte apoptosis. CKI markedly attenuated the expression of apoptosis-related proteins in the PI3K/Akt pathway. The results of the in vitro experiments indicated that CKI promoted cardiomyocyte proliferation and inhibited apoptosis, similar to LY294002. On the whole, the present study demonstrates that CKI reduces cardiomyocyte apoptosis, promotes healthy cardiac function and attenuates Ang II-mediated HF. These ameliorative effects may be associated with the inhibition of the PI3K/Akt pathway.

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Section: Discussionmentioning

confidence: 99%

Compound Kushen injection attenuates angiotensin II‑mediated heart failure by inhibiting the PI3K/Akt pathway

Wang

Yang

et al. 2023

Int J Mol Med

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“…The diversity of transporters encompassing ABC transporters, metal transporters (CNNM3/4), lactate transporters (SLC16A3), carboxylic acids transporters (SLC16A1/MTC) and SLC transporters (amino acid). S‐EV‐mediated horizontal transfer of membrane‐embedded drug efflux pumps to sensitive cancer cells is well‐known, leading to acquired drug resistance in vitro and in vivo (Bebawy et al., 2009 ; Levchenko et al., 2005 ; Lv et al., 2014 ; Sousa et al., 2015 ; Zhao et al., 2021 ). Besides their role in chemoresistance, membrane transporters also dictate organ tropism of circulating EVs (Wu et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Proteomic dissection of large extracellular vesicle surfaceome unravels interactive surface platform

Rai

Fang

Claridge

et al. 2021

J of Extracellular Vesicle

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The extracellular vesicle (EV) surface proteome (surfaceome) acts as a fundamental signalling gateway by bridging intra‐ and extracellular signalling networks, dictates EVs’ capacity to communicate and interact with their environment, and is a source of potential disease biomarkers and therapeutic targets. However, our understanding of surface protein composition of large EVs (L‐EVs, 100–800 nm, mean 310 nm, ATP5F1A, ATP5F1B, DHX9, GOT2, HSPA5, HSPD1, MDH2, STOML2), a major EV‐subtype that are distinct from small EVs (S‐EVs, 30–150 nm, mean 110 nm, CD44, CD63, CD81, CD82, CD9, PDCD6IP, SDCBP, TSG101) remains limited. Using a membrane impermeant derivative of biotin to capture surface proteins coupled to mass spectrometry analysis, we show that out of 4143 proteins identified in density‐gradient purified L‐EVs (1.07–1.11 g/mL, from multiple cancer cell lines), 961 proteins are surface accessible. The surface molecular diversity of L‐EVs include (i) bona fide plasma membrane anchored proteins (cluster of differentiation, transporters, receptors and GPI anchored proteins implicated in cell‐cell and cell‐ECM interactions); and (ii) membrane surface‐associated proteins (that are released by divalent ion chelator EDTA) implicated in actin cytoskeleton regulation, junction organization, glycolysis and platelet activation. Ligand‐receptor analysis of L‐EV surfaceome (e.g., ITGAV/ITGB1) uncovered interactome spanning 172 experimentally verified cognate binding partners (e.g., ANGPTL3, PLG, and VTN) with highest tissue enrichment for liver. Assessment of biotin inaccessible L‐EV proteome revealed enrichment for proteins belonging to COPI/II‐coated ER/Golgi‐derived vesicles and mitochondria. Additionally, despite common surface proteins identified in L‐EVs and S‐EVs, our data reveals surfaceome heterogeneity between the two EV‐subtype. Collectively, our study provides critical insights into diverse proteins operating at the interactive platform of L‐EVs and molecular leads for future studies seeking to decipher L‐EV heterogeneity and function.

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The Roles of Extracellular Vesicles and Circulating Noncoding RNAs in Laryngeal Cancer and Their Implication on Diagnosis, Prognosis, and Therapy

Ariyanon

Chattipakorn

2022

Interdisciplinary Cancer Research

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Effects of ATP-binding cassette transporter G2 in extracellular vesicles on drug resistance of laryngeal cancer cells in in vivo and in vitro

Cited by 6 publications

References 56 publications

Compound Kushen injection attenuates angiotensin II‑mediated heart failure by inhibiting the PI3K/Akt pathway

Compound Kushen injection attenuates angiotensin II‑mediated heart failure by inhibiting the PI3K/Akt pathway

Proteomic dissection of large extracellular vesicle surfaceome unravels interactive surface platform

The Roles of Extracellular Vesicles and Circulating Noncoding RNAs in Laryngeal Cancer and Their Implication on Diagnosis, Prognosis, and Therapy

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