Griffipavixanthone from Garcinia oblongifolia Champ Induces Cell Apoptosis in Human Non-Small-Cell Lung Cancer H520 Cells in Vitro

AbstractThe present study aims to investigate the mechanism of miR-384 in non-small cell lung cancer (NSCLC) cell apoptosis and autophagy by regulating Collagen α-1(X) chain (COL10A1). Bioinformatics methods were applied to evaluate potential miRNAs and genes that might correlate with NSCLC. Tumor tissues and adjacent tissues from 104 NSCLC patients were collected and human NSCLC A549 cell line was selected for subsequent experiments. A549 cells were treated with miR-384 mimic, miR-384 inhibitor, or knockdown of COL10A1. Quantitative real-time PCR (qRT-PCR) and Western blotting were utilized to detect the levels of miR-384, COL10A, Survivin, Bcl-2, Bax, Bcl-xl, Beclin 1, and LC3 in tissues and cells. A series of biological assays including MTT assay, Annexin V-FITC/PI (propidium iodide) staining, immunofluorescence, monodansylcadaverine (MDC) staining were conducted to investigate the effects of miR-384 and COL10A1 on NSCLC cells. Tumorigenicity assay for nude rats was applied. Results obtained from the present study indicated that miR-384 down-regulated COL10A1 by targetting it. Compared with adjacent tissues, miR-384 expression was obviously reduced while COL10A1 expression was significantly enhanced in NSCLC tissues (all P<0.05). Outcomes in vivo and in vitro suggested that cell proliferation and tumorigenicity were inhibited while cell apoptosis and autophagy were induced in NSCLC cells treated with up-regulation of miR-384 or silence of COL10A1. In miR-384 inhibitor group, cell proliferation was improved, while cell apoptosis was reduced and cell autophagy was decreased whereas tumorigenicity of cells was strengthened. Based on the findings of our study, it was established that miR-384 could down-regulate COL10A1 levels, subsequently inhibiting cell proliferation and promoting cell apoptosis and autophagy in NSCLC cells.

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Midazolam increases cisplatin-sensitivity in non-small cell lung cancer (NSCLC) via the miR-194-5p/HOOK3 axis

Cancer Cell International ◽

10.1186/s12935-021-02104-6 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Tingting Sun ◽

Jing Chen ◽

Xuechao Sun ◽

Guonian Wang

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Cell Apoptosis ◽

Cisplatin Resistance ◽

Small Cell ◽

Luciferase Reporter ◽

Small Cell Lung ◽

Cisplatin Sensitivity

Abstract Backgrounds As previously reported, midazolam anesthesia exerts tumor-suppressing effects in non-small cell lung cancer (NSCLC), but the regulating effects of this drug on cisplatin-resistance in NSCLC have not been studied. Thus, we designed this study to investigate this issue and preliminarily delineate the potential molecular mechanisms. Methods We performed MTT assay and trypan blue staining assay to measure cell proliferation and viability. Cell apoptosis was examined by FCM. qRT-PCR and immunoblotting were performed to determine the expression levels of genes. The targeting sites between genes were predicted by bioinformatics analysis and were validated by dual-luciferase reporter gene system assay. Mice tumor-bearing models were established and the tumorigenesis was evaluated by measuring tumor weight and volume. Immunohistochemistry (IHC) was used to examine the pro-proliferative Ki67 protein expressions in mice tumor tissues. Results The cisplatin-resistant NSCLC (CR-NSCLC) cells were treated with high-dose cisplatin (50 μg/ml) and low-dose midazolam (10 μg/ml), and the results showed that midazolam suppressed cell proliferation and viability, and promoted cell apoptosis in cisplatin-treated CR-NSCLC cells. In addition, midazolam enhanced cisplatin-sensitivity in CR-NSCLC cell via modulating the miR-194-5p/hook microtubule-tethering protein 3 (HOOK3) axis. Specifically, midazolam upregulated miR-194-5p, but downregulated HOOK3 in the CR-NSCLC cells, and further results validated that miR-194-5p bound to the 3’ untranslated region (3’UTR) of HOOK3 mRNA for its inhibition. Also, midazolam downregulated HOOK3 in CR-NSCLC cells by upregulating miR-194-5p. Functional experiments validated that both miR-194-5p downregulation and HOOK3 upregulation abrogated the promoting effects of midazolam on cisplatin-sensitivity in CR-NSCLC cells. Conclusions Taken together, this study found that midazolam anesthesia reduced cisplatin-resistance in CR-NSCLC cells by regulating the miR-194-5p/HOOK3 axis, implying that midazolam could be used as adjuvant drug for NSCLC treatment in clinical practices.

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Investigation of in vitro Activities of Cu2ZnSnS4 Nanoparticles in Human Non-Small Cell Lung Cancer

Materials Today Communications ◽

10.1016/j.mtcomm.2021.102304 ◽

2021 ◽

pp. 102304

Author(s):

Suleyman Gokhan Colak ◽

Canan Vejselova Sezer ◽

Ruken Esra Demirdogen ◽

Mine Ince ◽

Fatih Mehmet Emen ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung

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Elevating CDCA3 levels in non-small cell lung cancer enhances sensitivity to platinum-based chemotherapy

Communications Biology ◽

10.1038/s42003-021-02136-8 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Katrina Kildey ◽

Neha S. Gandhi ◽

Katherine B. Sahin ◽

Esha T. Shah ◽

Eric Boittier ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Genome Instability ◽

Small Cell ◽

Small Cell Lung ◽

Protein Levels ◽

Platinum Based Chemotherapy ◽

Platinum Agents

AbstractPlatinum-based chemotherapy remains the cornerstone of treatment for most non-small cell lung cancer (NSCLC) cases either as maintenance therapy or in combination with immunotherapy. However, resistance remains a primary issue. Our findings point to the possibility of exploiting levels of cell division cycle associated protein-3 (CDCA3) to improve response of NSCLC tumours to therapy. We demonstrate that in patients and in vitro analyses, CDCA3 levels correlate with measures of genome instability and platinum sensitivity, whereby CDCA3high tumours are sensitive to cisplatin and carboplatin. In NSCLC, CDCA3 protein levels are regulated by the ubiquitin ligase APC/C and cofactor Cdh1. Here, we identified that the degradation of CDCA3 is modulated by activity of casein kinase 2 (CK2) which promotes an interaction between CDCA3 and Cdh1. Supporting this, pharmacological inhibition of CK2 with CX-4945 disrupts CDCA3 degradation, elevating CDCA3 levels and increasing sensitivity to platinum agents. We propose that combining CK2 inhibitors with platinum-based chemotherapy could enhance platinum efficacy in CDCA3low NSCLC tumours and benefit patients.

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Inhibition of yes-associated protein suppresses migration, invasion, and metastasis in non-small cell lung cancer in vitro and in vivo

Clinical and Experimental Medicine ◽

10.1007/s10238-021-00738-4 ◽

2021 ◽

Author(s):

Tomoya Takeda ◽

Masanobu Tsubaki ◽

Shuji Genno ◽

Takuya Matsuda ◽

Yuuta Yamamoto ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Invasion And Metastasis ◽

Small Cell Lung

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Mimicking Tumor Hypoxia in Non-Small Cell Lung Cancer Employing Three-Dimensional In Vitro Models

Cells ◽

10.3390/cells10010141 ◽

2021 ◽

Vol 10 (1) ◽

pp. 141

Author(s):

Iwona Ziółkowska-Suchanek

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Tumor Hypoxia ◽

Three Dimensional ◽

In Vitro Models ◽

Small Cell ◽

Small Cell Lung ◽

Multicellular Tumor Spheroid

Hypoxia is the most common microenvironment feature of lung cancer tumors, which affects cancer progression, metastasis and metabolism. Oxygen induces both proteomic and genomic changes within tumor cells, which cause many alternations in the tumor microenvironment (TME). This review defines current knowledge in the field of tumor hypoxia in non-small cell lung cancer (NSCLC), including biology, biomarkers, in vitro and in vivo studies and also hypoxia imaging and detection. While classic two-dimensional (2D) in vitro research models reveal some hypoxia dependent manifestations, three-dimensional (3D) cell culture models more accurately replicate the hypoxic TME. In this study, a systematic review of the current NSCLC 3D models that have been able to mimic the hypoxic TME is presented. The multicellular tumor spheroid, organoids, scaffolds, microfluidic devices and 3D bioprinting currently being utilized in NSCLC hypoxia studies are reviewed. Additionally, the utilization of 3D in vitro models for exploring biological and therapeutic parameters in the future is described.

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Tumour-derived exosomal lncRNA-SOX2OT promotes bone metastasis of non-small cell lung cancer by targeting the miRNA-194-5p/RAC1 signalling axis in osteoclasts

Cell Death and Disease ◽

10.1038/s41419-021-03928-w ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Jianjiao Ni ◽

Xiaofei Zhang ◽

Juan Li ◽

Zhiqin Zheng ◽

Junhua Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Bone Metastasis ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Osteoclast Differentiation ◽

Small Cell ◽

Signalling Pathway ◽

Small Cell Lung

AbstractBone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.

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