scholarly journals Hyperbaric Oxygen Suppressed Tumor Progression through Improvement of Tumor Hypoxia and Induction of Tumor Apoptosis in Lung Cancer

2021 ◽  
Author(s):  
Shao-Yuan Chen ◽  
Koichi Tsuneyama ◽  
Mao-Hsiung Yen ◽  
Jiunn-Tay Lee ◽  
Jiun-Liang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cells ◽  
Hyperbaric Oxygen ◽  
Severe Combined Immunodeficiency ◽  
Tumor Hypoxia ◽  
A549 Cells ◽  
Oxygen Deficit ◽  
Dependent Manner ◽  
Xenograft Tumor ◽  
Tumor Models

Abstract Tumor cells have long term been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and have the potentials to be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Our results demonstrated that HBOT improved tissue vasculogenesis, tumor hypoxia and potentially target apoptosis to lung cancer cells in murine xenograft tumor models. HBOT will merit further cancer therapy as an adjuvant treatment for lung cancer.

scholarly journals Hyperbaric oxygen suppressed tumor progression through the improvement of tumor hypoxia and induction of tumor apoptosis in A549-cell-transferred lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shao-Yuan Chen ◽  
Koichi Tsuneyama ◽  
Mao-Hsiung Yen ◽  
Jiunn-Tay Lee ◽  
Jiun-Liang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Solid Tumors ◽  
Tumor Cells ◽  
Hyperbaric Oxygen ◽  
A549 Cell ◽  
P53 Protein ◽  
Tumor Hypoxia ◽  
A549 Cells ◽  
Xenograft Tumor ◽  
Tumor Models

AbstractTumor cells have long been recognized as a relative contraindication to hyperbaric oxygen treatment (HBOT) since HBOT might enhance progressive cancer growth. However, in an oxygen deficit condition, tumor cells are more progressive and can be metastatic. HBOT increasing in oxygen partial pressure may benefit tumor suppression. In this study, we investigated the effects of HBOT on solid tumors, such as lung cancer. Non-small cell human lung carcinoma A549-cell-transferred severe combined immunodeficiency mice (SCID) mice were selected as an in vivo model to detect the potential mechanism of HBOT in lung tumors. HBOT not only improved tumor hypoxia but also suppressed tumor growth in murine xenograft tumor models. Platelet endothelial cell adhesion molecule (PECAM-1/CD31) was significantly increased after HBOT. Immunostaining of cleaved caspase-3 was demonstrated and apoptotic tumor cells with nuclear debris were aggregated starting on the 14th-day after HBOT. In vitro, HBOT suppressed the growth of A549 cells in a time-dependent manner and immediately downregulated the expression of p53 protein after HBOT in A549 cells. Furthermore, HBOT-reduced p53 protein could be rescued by a proteasome degradation inhibitor, but not an autophagy inhibitor in A549 cells. Our results demonstrated that HBOT improved tissue angiogenesis, tumor hypoxia and increased tumor apoptosis to lung cancer cells in murine xenograft tumor models, through modifying the tumor hypoxic microenvironment. HBOT will merit further cancer therapy as an adjuvant treatment for solid tumors, such as lung cancer.

scholarly journals Cytotoxic Effects of Flubendazole in Human Lung Cancer Cell Line A549

2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Elham Hoveizi ◽  
Fatemeh Fakharzadeh Jahromi
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Human Lung ◽  
A549 Cells ◽  
Beclin 1 ◽  
Human Lung Cancer ◽  
Pcr Analysis ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Acridine Orange Staining

Background: The development of effective anticancer drugs is a significant health issue. Previous studies showed that members of the benzimidazole family have anticancer effects on several cancers Objectives: The present study investigated the cytotoxic effect of flubendazole on A549 human lung cancer cells. Methods: The A549 cells were treated with flubendazole at 1, 2, 5, and 10 µM concentrations for three days. Cell viability was measured by the MTT assay and Acridine orange staining. Also, the expressions of P62 and Beclin -1 were analyzed by qRT-PCR analysis. Results: Cell viability of A549 cells, in a concentration-dependent manner, showed significant differences between the treatment and control groups, and the IC50 value was determined to be 2 µM. Also, flubendazole reduced the expression of P62 and increased the expression of Beclin 1 in treated cells. Conclusions: Flubendazole induces cell death in A549 cells in a dose and time-dependent manner and can offer new factors in lung cancer therapeutic strategies.

Role of DACH1 on proliferation, invasion, and apoptosis in human lung adenocarcinoma cells

2021 ◽  
Vol 21 ◽  
Author(s):  
Junjie Yu ◽  
Ping Jiang ◽  
Ke Zhao ◽  
Zhiguo Chen ◽  
Tao Zuo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Tumor Cells ◽  
Human Lung ◽  
A549 Cells ◽  
Cancer Tissue ◽  
Lung Cancer Tissue ◽  
Adenocarcinoma Cells ◽  
Human Lung Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells

Objective: To investigate DACH1 protein expression in lung cancer tissue and matched paracancerous tissue, and explore its effect on proliferation, invasion, and apoptosis in human lung adenocarcinoma cells (HLACs). Methods: Tumor tissue and matched paracancerous tissue was collected from 46 patients with pathologically diagnosed lung cancer. RT-PCR was perfomed to detect DACH1 mRNA expression and immunohistochemistry to measured DACH1 protein expression. To determine the effect of DACH1 on lung cancer behavior, small interfering RNA (siRNA) was used to silence DACH1 expression in A549 cells. The impact on the proliferation of tumor cells was then observed by MTT assay, changes in the invasion of tumor cells were identified using transwell chamber assay, and the effects on apoptosis in the cell line were detected using flow cytometry. Results: The expression of DACH1 mRNA and DACH1 protein were significantly decreased in lung cancer tissue versus matched paracancerous control tissue. Silencing of DACH1 expression in A549 cells significantly enhanced cell proliferation, significantly increased cell invasion and significantly reduced spontaneous apoptosis. Conclusion: DACH1 is downregulated in lung adenocarcinoma tissue. In vitro assessment shows that DACH1 functions as a tumor suppressor, suggesting its potential use as new target for lung cancer treatment.

Synergy of nanodiamond-doxorubicin conjugates and PD-L1 blockade effectively turns tumor associated macrophages against tumor cells

2021 ◽  
Author(s):  
Huazhen Xu ◽  
Tongfei Li ◽  
Chao Wang ◽  
Yan Ma ◽  
Yan Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Lung Cancer Cells ◽  
Dependent Manner ◽  
Tumor Associated Macrophages ◽  
M1 Type

Abstract Background: Tumor-associated macrophages (TAM) are the most abundant stromal cells in the tumor microenvironment. Turning the TAM against their host tumor cells is an intriguing therapeutic strategy particularly attractive for patients with immunologically “cold” tumors. This concept was mechanistically demonstrated on in vitro human and murine lung cancer cells and their corresponding TAM models through combinatorial use of nanodiamond-doxorubicin conjugates (Nano-DOX) and a PD-L1 blocking agent BMS-1. Nano-DOX are an agent previously proved to be able to stimulate tumor cells’ immunogenicity and thereby reactivate the TAM into the anti-tumor M1 phenotype. Results: Nano-DOX were first shown to stimulate the tumor cells and the TAM to release the cytokine HMGB1 which, regardless of its source, acted through the RAGE/NF-κB pathway to induce PD-L1 in the tumor cells and PD-L1/PD-1 in the TAM. Interestingly, Nano-DOX also induced NF-κB-dependent RAGE expression in the tumor cells and thus reinforced HMGB1’s action thereon. Then, BMS-1 was shown to enhance Nano-DOX-stimulated M1-type activation of TAM both by blocking Nano-DOX-induced PD-L1 in the TAM and by blocking tumor cell PD-L1 ligation with TAM PD-1. The TAM with enhanced M1-type repolarization both killed the tumor cells and suppressed their growth. BMS-1 could also potentiate Nano-DOX’s action to suppress tumor cell growth via blocking of Nano-DOX-induced PD-L1 therein. Finally, Nano-DOX and BMS-1 achieved synergistic therapeutic efficacy against in vivo tumor grafts in a TAM-dependent manner. Conclusions: PD-L1/PD-1 upregulation mediated by autocrine and paracrine activation of the HMGB1/RAGE/NF-κB signaling is a key response of lung cancer cells and their TAM to stress, which can be induced by Nano-DOX. Blockade of Nano-DOX-induced PD-L1, both in the cancer cells and the TAM, achieves enhanced activation of TAM-mediated anti-tumor response.

Abstract 646: Feasibility of assessing circulating tumor cells in patient-derived xenograft tumor models

2016 ◽  
Author(s):  
Somdutta Roy ◽  
Kevin Martinez ◽  
Arturo Ramirez ◽  
Daniel Campton ◽  
Joshua Nordberg ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Xenograft Tumor ◽  
Tumor Models ◽  
Patient Derived Xenograft

scholarly journals A dose- and time-dependent effect of oxythiamine on cell growth inhibition in non-small cell lung cancer

2021 ◽  
Author(s):  
Lin Bai ◽  
Hui-li Zhu
Keyword(s):  
Lung Cancer ◽  
Cell Growth ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Critical Role ◽  
A549 Cells ◽  
Small Cell ◽  
Time Dependent ◽  
Dependent Manner ◽  
Small Cell Lung

AbstractThe high mortality rate of non-small-cell lung cancer (NSCLC) is mostly due to the high risk of recurrence. A comprehensive understanding of proliferation mechanisms of NSCLC would remarkably contribute to blocking up the invasion and metastasis of tumor cells. In our previous study, the remarkable decreased activity of Thiamine-dependent enzymes (TDEs), involving in intermediary metabolism responsible for energy production of tumor, was found under conditions of thiamine deficiency in vivo. To explore the effect of Oxythiamine (OT), a TDEs antimetabolite, on cell growth, we co-cultured A549 cells with OT in vitro at various doses (0.1, 1, 10 and 100 μM) and time periods (6, 12, 24 and 48 h) and subsequent cell proliferation and apoptosis assays were performed respectively. Our findings demonstrated that A549 cells proliferation was significantly downregulated by OT treatment in a progressively dose as well as time dependent manner. Inhibition of TDEs resulted in antagonism of lung cancer growth by inducing cells to cease the cycle as well as apoptotic cell death. We concluded a critical role of OT, a TDEs antagonistic compound, indicating the potential target of its practical use.

scholarly journals EVALUATION OF IN VITRO CYTOTOXIC EFFECT OF VIOLACEIN PRODUCED BY NOVEL ISOLATE CHROMOBACTERIUM VACCINII CV5 AGAINST THE CERVICAL AND LUNG CANCER CELL

2017 ◽  
Vol 10 (10) ◽  
pp. 227 ◽  
Author(s):  
Vishnu T Santhosh ◽  
Palaniswamy Muthusamy
Keyword(s):  
Lung Cancer ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Cancer Cell ◽  
A549 Cells ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Cytotoxicity Activity ◽  
Ic50 Values

  Objectives: This study investigates the in vitro anticancer activity of the violacein extracted from the Chromobacterium vaccinii CV5.Methods: Natural colorants or dyes derived from flora to fauna are believed to be safe because of nontoxic, noncarcinogenic, and biodegradable in nature. There are a number of natural pigments, but only a few are available in sufficient quantities for industrial production. The cytotoxicity activity of pigment was assessed against the cervical (HeLa) and lung cancer (A549) cell lines using the MTT assay and there by potential cytotoxic activity exhibited by the pigment was identified.Results: The result of the pigment shows potent anticancer activity on the two cancer cell lines tested in a concentration dependent manner. The potent anticancer activity was observed with the pigment with IC50 values of 26 μg/mL on HeLa and 31 μg/mL on A549 cells, respectively.Conclusion: The study is pioneering report for determining the better in vitro anticancer activity of violacein from the novel isolate C. vaccinii CV5.

454 Oncolytic parainfluenza virus 5 vector enhances natural killer cell killing of lung tumor cells in 2D and 3D spheroid cultures

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A481-A481
Author(s):  
Namita Varudkar ◽  
Jeremiah Oyer ◽  
Alicja Copik ◽  
Griffith Parks
Keyword(s):  
Lung Cancer ◽  
Nk Cells ◽  
Natural Killer ◽  
Tumor Cells ◽  
Immune Cells ◽  
Nk Cell ◽  
Lung Tumor ◽  
A549 Cells ◽  
Live Cell ◽  
Parainfluenza Virus

BackgroundNatural killer (NK) cells are innate immune cells with natural cytotoxicity towards both tumor cells and virus infected cells. We have developed a particle-based method for in vitro specific expansion of NK cells that yields highly cytotoxic NK cells (PM21-NK cells). There is intense interest in the use of novel oncolytic viruses with the potential to synergize with immune cells to kill tumor cells. Here we have tested the hypothesis that infection with a tumor-selective cytopathic Parainfluenza virus 5 (PIV5-P/V) vector will enhance PM21-NK cell-mediated killing of lung cancer cells in both 2-dimensional (2D) and 3-dimensional (3D) cultures.MethodsIn 2D cultures, live cell time-lapse imaging, flow cytometry and luminescence-based methods were used to assess the killing efficiency of PM21-NK cells against A549 lung tumor cells infected with PIV5-P/V. Blocking antibodies were used to evaluate different NK cell activating receptors involved in recognition of infected tumor cells. IncuCyte live cell imaging system was used to assess real time killing of 3D lung spheroids by a combination of NK cells and PIV5-P/V virus. Z-stack spheroid images were captured using Keyence microscope.ResultsIn 2D cultures, PM21 NK cells efficiently kill A549 cells that have been infected with P/V CPI- virus and enhance the overall rate of killing compared to uninfected cell targets. Antibody blocking showed that the viral Hemagglutinin-Neuraminidase (HN) glycoprotein and NK cell receptors NKp30, NKp46 and NKG2D were involved in PM21-NK cell recognition of PIV5-P/V infected A549 cells. In 3D cultures of A549 tumor spheroids, PIV5-P/V infection was limited to the outer layer of the spheroid, with restricted spread of the infection to inner compartments. However, addition of PM21-NK cells to PIV5-P/V-infected spheroids resulted in killing of not only the infected surface of the spheroid but continued to the uninfected cells located at the center of the spheroid.ConclusionsOur data support the potential of combining oncolytic virotherapy along with PM21-NK cell adoptive therapy against lung cancer.

scholarly journals (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) induces apoptosis via the intrinsic pathway in H1299 lung cancer cells

2017 ◽  
Author(s):  
Jong-Woon Shin ◽  
Sae-Bom Kwon ◽  
Yesol Bak ◽  
Sangku Lee ◽  
Do-Young Yoon
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Morphological Changes ◽  
A549 Cells ◽  
Fluorescein Isothiocyanate ◽  
Receptor Expression ◽  
Dependent Manner ◽  
Intrinsic Pathway ◽  
Extrinsic Pathway ◽  
Dose Dependent

Abstract(E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI) is known as a dual specific phosphatase 1/6 or MAPK inhibitor. However, its precise anti-lung cancer mechanism remains unknown. In this study, the effects of BCI on cell viability were investigated in the non-small cell lung cancer cell lines NCI-H1299, A549, and NCI-H460. We confirmed that BCI significantly inhibited the cell viability of NCI-H1299 compared to those of NCI-H460 and A549 cells. The anti-cancer effects of BCI were evaluated by MTS assay, annexin V-fluorescein isothiocyanate/propidium iodide staining, cell cycle analysis, reverse transcription-PCR, western blotting, and JC-1 staining in NCI-H1299 cells. BCI induced cellular morphological changes and inhibited viability of NCI-H1299 cells in a dose-dependent manner. BCI enhanced Bax expression and induced processing of caspase-9, caspase-3, and poly (ADP-ribose) polymerase as well as the release of cytochrome c from the mitochondria into the cytosol. BCI also down-regulated Bcl-2 expression but enhanced Bax expression in a dose-dependent manner in NCI-H1299 cells. In addition, BCI did not modulate death receptor expression or the extrinsic factor caspase-8 and Bid, a linker between the intrinsic and extrinsic apoptotic pathways in NCI-H1299 cells. On the basis of these results, we conclude that BCI induces apoptosis through a mediated intrinsic pathway, but not extrinsic pathway in NCI-H1299 cells. These results suggest that BCI can be used as a therapeutic agent in lung cancer.

scholarly journals Up-Regulation of p53/miR-628-3p Pathway, a Novel Mechanism of Shikonin on Inhibiting Proliferation and Inducing Apoptosis of A549 and PC-9 Non–Small Cell Lung Cancer Cell Lines

2021 ◽  
Vol 12 ◽  
Author(s):  
Jieli Pan ◽  
Meiya Li ◽  
Fenglin Yu ◽  
Feiye Zhu ◽  
Linyan Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Treatment Strategies ◽  
A549 Cells ◽  
Direct Interaction ◽  
Promoter Sequence ◽  
Small Cell ◽  
Dependent Manner ◽  
Small Cell Lung

Shikonin (SHK) is a pleiotropic agent with remarkable cell growth inhibition activity against various cancer types, especially non–small cell lung cancer (NSCLC), but its molecular mechanism is still unclear. Our previous study found that miR-628-3p could inhibit the growth of A549 cells and induce its apoptosis. Bioinformatics analysis predicted that miR-628-3p promoter sequence contained p53 binding sites. Considering the regulatory effect of SHK on p53, we speculate that SHK may inhibit the growth and induce apoptosis of NSCLC cells by up-regulating miR-628-3p. CCK-8 and EdU assay confirmed the inhibitory effect of SHK on A549 and PC-9 cells. Meanwhile, quantitative reverse transcription–polymerase chain reaction and Western blot showed that SHK could promote the expression of p53 and miR-628-3p in a dose-dependent manner. Overexpression of p53 or miR-628-3p can inhibit the growth and promote apoptosis of A549 and PC-9 cells, while silencing p53 or miR-628-3p has the opposite effect. Dual luciferase reporting assay and ChIP (chromatin immunoprecipitation) assay further verified the direct interaction between p53 and the promoter of miR-628-3p. Gene knockdown for p53 or miR-628-3p confirmed that SHK inhibits the growth and induces apoptosis of A549 and PC-9 cells at least partly by up-regulating p53/miR-628-3p signaling pathway. Therefore, these novel findings provide an alternative approach to target p53/miR-628-3p axis and could be used for the development of new treatment strategies for NSCLC.

Sign in / Sign up

Export Citation Format

Share Document