The roles of extracellular vesicles in gastric cancer development, microenvironment, anti-cancer drug resistance, and therapy

Huang, Tingting; Song, Chunli; Zheng, Lei; Xia, Ligang; Yang, Li; Zhou, Yiwen

doi:10.1186/s12943-019-0967-5

Cited by 127 publications

(99 citation statements)

References 70 publications

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“…While exosomes are small membrane nanovesicles which constituted through the intraluminal budding of the late endosomal membrane and are secreted from the plasma membrane. [107][108][109] Recently, the finding that paclitaxel-resistant gastric cancer cell line (MGC-803R) cell-derived exosomes could be taken up by paclitaxel-sensitive MGC-803 (MGC-803S) cells has been reported. Furthermore, the exosomal miR-155-5p from MGC-803R cells can join in directly inhibiting GATA binding protein 3 (GATA3) and tumor protein p53-inducible nuclear protein 1 (TP53INP1) to induce chemoresistant phenotypes in the sensitive cells which uptake the exosomes.…”

Section: Extracellular Vesicles and Micropinocytosismentioning

confidence: 99%

A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer

Ruan¹,

Liu²,

Tao³

et al. 2020

OTT

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Gastric cancer is one of the most common malignant tumors, and it is also one of the leading causes of cancer death worldwide. Because of its insidious symptoms and lack of early dictation screening, many cases of gastric cancer are at late stages which make it more complicated to cure. For these advanced-stage gastric cancers, combination therapy of surgery, chemotherapy, radiotherapy and target therapy would bring more benefit to the patients. However, the drug-resistance to the chemotherapy restricts its effect and might lead to treatment failure. In this review article, we discuss the mechanisms which have been found in recent years of drug resistance in gastric cancer. And we also want to find new approaches to counteract chemotherapy resistance and bring more benefits to the patients.

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Section: Extracellular Vesicles and Micropinocytosismentioning

confidence: 99%

A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer

Ruan¹,

Liu²,

Tao³

et al. 2020

OTT

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“…Cancer is the second leading cause of death worldwide, among which gastric cancer (GC) is one of the most common malignancies of the digestive system, ranking second in cancer-related mortality [1]. The main causes of GC death are rapid proliferation, invasion, metastasis, and anti-cancer drug resistance [2,3]. The prognosis of patients can be significantly improved by the combination of radiotherapy, neoadjuvant therapy, and other treatment measures [4,5].…”

Section: Introductionmentioning

confidence: 99%

KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis

Ding

et al. 2020

Cancer Cell Int

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Background: Kinesin superfamily proteins (KIFs) can transport membranous organelles and protein complexes in an ATP-dependent manner. Kinesin family member 15 (KIF15) is overexpressed in various cancers. However, the function of KIF15 in gastric cancer (GC) is still unclear. Methods: GC patients' data from The Cancer Genome Atlas (TCGA) were analyzed by bioinformatics methods. The expression of KIF15 was examined in GC and paracarcinoma tissues from 41 patients to verify the analysis results. The relationship between KIF15 expression and clinical characteristics were also observed by bioinformatics methods. Kaplan-Meier survival analysis of 122 GC patients in our hospital was performed to explore the relationship between KIF15 expression levels and GC patients' prognosis. KIF15 was downregulated in GC cell lines AGS and SGC-7901 by transfecting a lentivirus-mediated shRNA plasmid targeting KIF15. In vitro, GC cell proliferation and apoptosis were detected by MTT assay, colony formation assay, and Annexin V-APC staining. In vivo, xenograft experiments were used to verify the in vitro results. Furthermore, Human Apoptosis Antibody Array kit was used to screen possible targets of KIF15 in GC cell lines. Results: The bioinformatics results showed that KIF15 expression levels were higher in GC tissues than in normal tissues. IHC showed same results. High expression of KIF15 was statistical correlated with high age and early histologic stage. Kaplan-Meier curves indicated that high KIF15 expression predict poor prognosis in patients with GC. MTT assay and colony formation assay showed that KIF15 promote GC cell proliferation. Annexin V-APC staining found that KIF15 can inhibit GC cell apoptosis. Xenograft experiments reveal that downregulating KIF15 can inhibit GC tumor growth and promote GC apoptosis. Through detection of 43 anti-apoptotic proteins by the Human Apoptosis Antibody Array kit, it was confirmed that knocking down KIF15 can reduce seven anti-apoptotic proteins expression. Conclusions: Taken together, our study revealed a critical role for KIF15 to inhibit GC cell apoptosis and promote GC cell proliferation. KIF15 may decrease anti-apoptotic proteins expression by regulating apoptosis pathways. High expression of KIF15 predicts a poor prognosis in patients with GC. KIF15 might be a novel prognostic biomarker and a therapeutic target for GC.

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“…4 In addition, development of drug resistance, disease relapse, and severe side effects of therapies contribute to morbidity and mortality in gastric cancer patients. 5 Therefore, these major clinical challenges urgently require new and safe treatment options.…”

Section: Introductionmentioning

confidence: 99%

Allylated Curcumin Analog CA6 Inhibits TrxR1 and Leads to ROS-Dependent Apoptotic Cell Death in Gastric Cancer Through Akt-FoxO3a

Rajamanickam

Yan

et al. 2020

CMAR

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Background: Gastric cancer is one of the leading causes of cancer-related deaths. Allylated monocarbonyl analogs of curcumin (MACs) have been reported to selectively inhibit a broad range of human cancers including gastric cancer. However, the precise molecular mechanisms underlying the inhibitory activities of MACs are not fully known. Methods: In this study, we examined the anti-tumor activities of an allylated MAC, CA6, on gastric cancer cells and gastric cancer xenograft mouse model. The potential molecular antitumor mechanisms of CA6 were also elucidated. Results: Our data show that CA6 exhibited significant cytotoxicity in gastric cancer cells, which was seen as an induction of G2/M cell cycle arrest and apoptosis. These activities were mediated through an elaboration of ROS levels in gastric cancer cells and induction of endoplasmic reticulum stress. CA6 increased ROS levels through directly binding to and inhibiting thioredoxin reductase R1 (TrxR1). Also, CA6-generated ROS inhibited Akt and activated forkhead O3A (FoxO3a), causing cytotoxicity in gastric cancer cells. Finally, CA6 treatment dose-dependently reduced the growth of gastric cancer xenografts in tumor-bearing mice, which was associated with reduced TrxR1 activity and increased ROS in the tumor. Conclusion: In summary, our studies demonstrate that CA6 inhibited gastric cancer growth by inhibiting TrxR1 and increasing ROS, which in turn activated FoxO3a through suppressing Akt. CA6 is a potential candidate for the treatment of gastric cancer.

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The roles of extracellular vesicles in gastric cancer development, microenvironment, anti-cancer drug resistance, and therapy

Cited by 127 publications

References 70 publications

<p>A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer</p>

<p>A Review of Research Progress in Multidrug-Resistance Mechanisms in Gastric Cancer</p>

KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis

<p>Allylated Curcumin Analog CA6 Inhibits TrxR1 and Leads to ROS-Dependent Apoptotic Cell Death in Gastric Cancer Through Akt-FoxO3a</p>

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