Knockdown of PD-L1 in Human Gastric Cancer Cells Inhibits Tumor Progression and Improves the Cytotoxic Sensitivity to CIK Therapy

Li, Jing; Chen, Lüjun; Xiong, Yuqi; Zheng, Xiao; Xie, Quanqin; Zhou, Qi; Shi, Liangrong; Wu, Changping; Jiang, Jingting; Wang, Haitao

doi:10.1159/000460504

Cited by 89 publications

(77 citation statements)

References 41 publications

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“…PD-L1 is the major ligand and is expressed on a variety of cell types, importantly including many tumors such as lung cancer. Previous studies have reported that the PD-1/PD-L1 system is involved in tumor immunity and is closely associated with tumorigenesis and invasiveness [28-31]. Increased expression of PD-L1 is significantly associated with poor prognosis in many cancers.…”

Section: Discussionmentioning

confidence: 99%

MiR-140 Expression Regulates Cell Proliferation and Targets PD-L1 in NSCLC

Xie

Liang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Programmed death ligand1(PD-L1) plays a role in the development and progression of non-small cell lung cancer (NSCLC). This study aimed to identify miRNA(s) that are responsible for regulation of expression of PD-L1 in NSCLC, and to investigate the role of PD-L1 in regulation of the cell cycle in NSCLC. Methods: We predicted the target miRNA of PD-L1, which was miR-140, using the online tools TargetScan and miBase. In NSCLC cells obtained from clinical specimens, in addition to A549 and NCI-H1650 cell cultures, western blots were used to detect the level of expression of proteins, while real-time PCR was used to determine the level of expression of PD-L1, miR-140, cyclin E, and β-actin. Transfection with miR-140 mimics, miR-140 inhibitors, and PD-L1 siRNA were conducted using commercial kits. To determine whether miR-140 directly binds PD-L1, a luciferase reporter gene with wild type or mutated PD-L1 was used. Cell viability was measured with the MTT assay, and PI staining was used for cell cycle analysis. Results: We found low expression of miR-140 and high expression of PD-L1 and cyclin E in NSCLC cells. Over-expression of miR-140 suppressed the expression of PD-L1 by directly binding its 3’ UTR, and was also associated with decreased expression of cyclin E and inhibition of cellular proliferation in A549 and NCI-H1650 cells. Inhibition of PD-L1, in the absence of manipulations to miR-140, also decreased the expression of cyclin E. Conclusion: We conclude that miR-140 directly suppresses PD-L1 and inhibits the miR-140/PD-L1/cyclin E pathway in NSCLC.

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Section: Discussionmentioning

confidence: 99%

MiR-140 Expression Regulates Cell Proliferation and Targets PD-L1 in NSCLC

Xie

Liang

et al. 2018

Cell Physiol Biochem

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“…PD-1 can be combined with PD-L1 and PD-L2 to inhibit the tumor microenvironment, tumor-specific T cell function, and immune surveillance function and promote tumor cell growth. 55,56 De Guillebon et al 57 evaluated the efficacy and safety of the PD-1 monoclonal antibody pembrolizumab for the treatment of advanced gastric cancer. The results showed that the response rate was 33%, the median response duration was 24 weeks, the 6-month PFS rate was 24%, and the 6-month OS rate was 69%.…”

Section: Immunotherapymentioning

confidence: 99%

Progress in the treatment of advanced gastric cancer

et al. 2017

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Gastric cancer is one of the most common malignant tumors in the digestive system. Surgery is currently considered to be the only radical treatment. As surgical techniques improve and progress is made in traditional radiotherapy, chemotherapy, and the implementation of neoadjuvant therapy, the 5-year survival rate of early gastric cancer can reach >95%. However, the low rate of early diagnosis means that most patients have advanced-stage disease at diagnosis and so the best surgical window is missed. Therefore, the main treatment for advanced gastric cancer is the combination of neoadjuvant chemoradiotherapy, molecular-targeted therapy, and immunotherapy. In this article, we summarize several common methods used to treat advanced gastric cancer and discuss the progress made in the treatment of gastric cancer in detail. Only clinical practice and clinical research will allow us to prolong the survival time of patients and allow the patients to truly benefit by paying attention to the individual patient characteristics, drug choice, and developing a reasonable and comprehensive treatment plan.

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“…Cells in which the nucleus was stained with fluorescein-dUTP were defined as TUNEL positive. The slides were then measured under a confocal microscope [28].…”

Section: Mitochondrial Membrane Potential (δψM) Atp Production and Mmentioning

confidence: 99%

Effect of Mst1 on Endometriosis Apoptosis and Migration: Role of Drp1-Related Mitochondrial Fission and Parkin-Required Mitophagy

Zhao

Yang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Mitochondrial homeostasis is implicated in the development and progression of endometriosis through poorly defined mechanisms. Mst1 is the major growth suppressor related to cancer migration, apoptosis and proliferation. However, whether Mst1 is involved in endometriosis apoptosis and migration via regulating the mitochondrial function remains to be elucidated. Methods: Expression of Mst1 in endometriosis was examined via western blots. Cellular apoptosis was detected via MTT and TUNEL assay. Gain of function assay about Mst1 was conducted via adenovirus over-expression. Mitochondrial functions were evaluated via mitochondrial membrane potential JC-1 staining, ROS flow cytometry analysis, mPTP opening assessment and immunofluorescence of HtrA2/Omi. The mitophagy activity were examined via western blots and immunofluorescence. Results: First, we found that Mst1 was significantly downregulated in the ectopic endometrium of endometriosis compared to the normal endometrium. However, the recovery of Mst1 function was closely associated with the inability of endometrial stromal cells (ESCs) to migrate and survive. A functional study indicated that regaining Mst1 enhanced Drp1 post-transcriptional phosphorylation at Ser616 and repressed Parkin transcription activity via p53, leading to mitochondrial fission activation and mitophagy inhibition. Excessive Drp1-related fission forced the mitochondria to liberate HtrA2/Omi into the cytoplasm. Moreover, Mst1-induced defective mitophagy evoked cellular

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Knockdown of PD-L1 in Human Gastric Cancer Cells Inhibits Tumor Progression and Improves the Cytotoxic Sensitivity to CIK Therapy

Cited by 89 publications

References 41 publications

MiR-140 Expression Regulates Cell Proliferation and Targets PD-L1 in NSCLC

MiR-140 Expression Regulates Cell Proliferation and Targets PD-L1 in NSCLC

Progress in the treatment of advanced gastric cancer

Effect of Mst1 on Endometriosis Apoptosis and Migration: Role of Drp1-Related Mitochondrial Fission and Parkin-Required Mitophagy

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