scholarly journals Oridonin Improves the Therapeutic Effect of Lentinan on Lung Cancer

2021 ◽  
Author(s):  
Yun Gui ◽  
Jing Cheng ◽  
Zhiguo Chen
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Cell Viability ◽  
Cell Line ◽  
A549 Cell ◽  
A549 Cells ◽  
Cancer Drug ◽  
Mice Model ◽  
Antitumor Effects ◽  
Mrna And Protein Expression

Abstract Oridonin, a compound from Rabdosia rubescens, has been shown to have a potency for the improvement of the antitumor effect of lentinan (LNT). In this study, we tested the effect of oridonin, LNT, and the combination of them on a normal human fetal lung fibroblast cell line MRC-5 and non-small cell lung cancer cell line A549. Then we tested their effects on metastasis and survival with a lung cancer mice model. The effects of them on the mRNA and protein expression of several regulatory factors in A549 and lung tissue were determined by QPCR and western blotting. Results showed that the viability of MRC-5 and A549 were not affected by 0-20 µg/ml oridonin. 0-300 µg/ml LNT did not affect the viability of MRC-5, but 50-400 µg/ml LNT inhibited the viability of A549. 20 µg/ml oridonin and 100 or 300 µg/ml LNT were used in the subsequent study. The oridonin, LNT, or the combination of both had no effect on MRC-5 cell viability. The oridonin had no effect on A549 cell viability but LNT suppressed A549 cell viability, and oridonin promoted the suppression of LNT on A549 cells. In vivo study showed that oridonin alone had no effect on metastasis and survival but LNT decreased metastasis and survival in mice. Oridonin improved the suppression of LNT against metastasis and further improved the survival rate. In both A549 and lung tissues, LNT increased the mRNA and protein expression of caspase-3, caspase-8, caspase-9, Bax, p53, p21, and IκB-α, reduced mRNA and protein expressions of Bcl-2 and NF-κB. Oridonin enhanced all the effects of LNT on cells. Our study demonstrated that oridonin enhanced the antitumor effects of LNT and is conducive to the development of oridonin and LNT as a novel cancer drug regimen.

scholarly journals Targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy

Biology Open ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. bio053298
Author(s):  
Jingjing Wu ◽  
Youqile Wu ◽  
Xuemei Lian
Keyword(s):  
Lung Cancer ◽  
Protein Expression ◽  
Cell Viability ◽  
Er Stress ◽  
Cancer Cells ◽  
Lung Tumor ◽  
Lung Cancer Cells ◽  
Dependent Manner ◽  
Mice Model ◽  
Targeted Inhibition

ABSTRACTThis study investigated the pathophysiological role of GRP78 in the survival of lung cancer cells. Lung cancer patient data from public databases were used to analyze the expression of GRP78 and its influence on prognoses. In vivo, GRP78 protein expression was analyzed in an established urethane-induced lung tumor mouse model. In vitro, the effects of targeted inhibition of GRP78 by HA15 in lung cancer cells were assessed, with cell viability analyzed using a CCK-8 assay, cell proliferation using an EdU assay, apoptosis and cell cycle using flow cytometry, subcellular structure using electron microscopy, and relative mRNA and protein expression using RT-PCR, western blotting or immunofluorescence assays. The results showed that GRP78 was highly expressed in the lung tissue of lung cancer mice model or patients, and was associated with a poor prognosis. After inhibition of GRP78 in lung cancer cells by HA15, cell viability was decreased in a dose- and time-dependent manner, proliferation was suppressed and apoptosis promoted. Unfolded protein response signaling pathway proteins were activated, and the autophagy-related proteins and mRNAs were upregulated. Therefore, targeted inhibition of GRP78 by HA15 promotes apoptosis of lung cancer cells accompanied by ER stress and autophagy.

scholarly journals Propofol Inhibits Lung Cancer A549 Cell Growth and Epithelial‐Mesenchymal Transition Process by Upregulation of MicroRNA-1284

2018 ◽  
Vol 27 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Wei-Zhen Liu ◽  
Nian Liu
Keyword(s):  
Lung Cancer ◽  
Cell Viability ◽  
Cancer Cells ◽  
A549 Cell ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Lung Cancer Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Foxm1 Expression

Propofol has been widely used in lung cancer resections. Some studies have demonstrated that the effects of propofol might be mediated by microRNAs (miRNAs). This study aimed to investigate the effects and mechanisms of propofol on lung cancer cells by regulation of miR-1284. A549 cells were treated with different concentrations of propofol, while transfected with miR-1284 inhibitor, si-FOXM1, and their negative controls. Cell viability, migration, and invasion, and the expression of miR-1284, FOXM1, and epithelial‐mesenchymal transition (EMT) factors were detected by CCK-8, Transwell, qRT-PCR, and Western blot assays, respectively. In addition, the regulatory and binding relationships among propofol, miR-1284, and FOXM1 were assessed, respectively. Results showed that propofol suppressed A549 cell viability, migration, and invasion, upregulated E-cadherin, and downregulated N-cadherin, vimentin, and Snail expressions. Moreover, propofol significantly promoted the expression of miR-1284. miR-1284 suppression abolished propofol-induced decreases of cell viability, migration, and invasion, and increased FOXM1 expression and the luciferase activity of FOXM1-wt. Further, miR-1284 negatively regulated FOXM1 expression. FOXM1 knockdown reduced cell viability, migration, and invasion by propofol treatment plus miR-1284 suppression. In conclusion, our study indicated that propofol could inhibit cell viability, migration, invasion, and the EMT process in lung cancer cells by regulation of miR-1284.

scholarly journals Silibinin Inhibits TGF-β-induced MMP-2 and MMP-9 Through Smad Signaling Pathway in Colorectal Cancer HT-29 Cells

2021 ◽  
Author(s):  
Zahra Zare ◽  
Tina Nayerpour dizaj ◽  
Armaghan Lohrasbi ◽  
Zakieh Sadat Sheikhalishahi ◽  
Amirhooman Asadi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Protein Expression ◽  
Cell Viability ◽  
Cancer Cells ◽  
Cell Line ◽  
Dependent Manner ◽  
Smad2 Phosphorylation ◽  
Mrna And Protein Expression ◽  
Dose Dependent ◽  
Ht 29

Background: Metastasis of cancer cells is the primary responsible for death in patients with colorectal cancer (CRC). Transforming growth factor-β (TGF-β)-induced matrix metalloproteinases (MMPs) are essential for the metastasis process. Silibinin is a natural compound extracted from the Silybum marianum that exhibits anti-neoplastic activity in cancer cell lines. In this study, we evaluated the effects of silibinin on MMP-2 and MMP-9 induced by TGF-β in human HT-29 CRC cell line and the potential mechanism underlying the effects. Methods: The present in vitro study was done on the HT-29 cell line. The HT-29 cell line was cultured in RPMI1640 and exposed to TGF- β (5 ng/ml) in the absence and presence of different concentrations of silibinin (10, 25, 50, and 100 μM). The effect of silibinin on HT-29 cell viability was measured with the MTT assay. A real-time polymerase chain reaction (Real-Time PCR) determined the relative mRNA expression of MMP-2 and MMP-9. Western blotting was employed to examine MMP-2 and MMP 9 protein expression and Smad2 phosphorylation. Results: Silibinin inhibits cell viability of HT-29 cell line at 24 hours in a dose-dependent manner. TGF-β increased the mRNA and protein expression of MMP-2, MMP-9, and phosphorylated Smad2 compared to controls. Pharmacological inhibition with silibinin markedly blocked TGF-β–induced MMP-2 and MMP-9 mRNA and protein expression and Smad2 phosphorylation. Conclusion: Silibinin decreased the cell viability of HT-29 cancer cells in a dose-dependent manner. Silibinin also inhibited TGF-β-stimulated MMP-2 and MMP-9 expression in HT-29 cells, possibly mediated with the Smad2 signaling pathway.

The effect of antisense oligodeoxynucleotides targeting Aurora A kinase on cell proliferation and chemosensitivity to paclitaxel in human lung cancer cell line A549

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21147-21147
Author(s):  
R. Meng ◽  
G. Wu ◽  
K. Y. Yang ◽  
J. Cheng
Keyword(s):  
Lung Cancer ◽  
Cell Line ◽  
A549 Cells ◽  
Cancer Cell Line ◽  
Lung Cancer Cell Line ◽  
Human Lung Cancer ◽  
Aurora A ◽  
Lung Cancer Cell ◽  
Mrna And Protein Expression ◽  
Cell Inhibition

21147 Background: Aurora kinases representing a family of evolutionarily conserved mitotic serine/threonine kinases have been found elevated in lung andenocarcinoma cell line A549. It is suggested that the overexpression of Aurora A contributes to the carcinogenesis, chromosomal instability (CIN), and de-differentiation of lung cancers. To address its possibility as a therapeutic target for lung cancer, we employed the antisense oligodeoxynucleotide (ASODN) technique to inhibit Aurora A expression and investegate its effect on tumor growth and cell cycle of A549, as well as the chemosensitivity of paclitaxel. Methods: Aurora A ASODN was synthesized and transfected into A549 cells by lipofectAMINE 2000.Aurora A mRNA and protein expression were examined by reverse transcription -polymerase chain reaction (RT-PCR) and Western blot respectively.Cell cycle distribution was observed by flow cytometer.MTT assay was used to evaluate cell inhibition ratio before and after transfection. Results: The proliferation of the A549 cells was inhibited by Aurora A ASODN dose and time dependently. It was also observed that the IC50 of A549 cells after 48 hours’ treatment of ASODN was about 300nmol/L and under such circumstances, the Aurora A mRNA and protein expression significantly decreased (P<0.05), along with the induction of accumulation of cells in S phase and the G2-M transition. Furhermore, cell inhibition ratio of the combination of Aurora A ASODN and paclitaxel was higher significantly than paclitaxel(P<0.05) or Aurora A ASODN alone (P<0.05). Conclusions: Inhibition of Aurora A expression can results in the suppression of cell growth and chemosensitizing activity to paclitaxel in human lung cancer cell line A549. No significant financial relationships to disclose.

scholarly journals Mechanism underlying the inhibitory effect of Elaeagnus Conferta Roxb on TNF –α induced NF- kB nuclear translocation in non- small lung cancer A549 cell line using Flow cytometry

2020 ◽  
Vol 11 (11) ◽  
pp. 260-268
Author(s):  
Lalitha G. ◽  
Nazeema TH
Keyword(s):  
Lung Cancer ◽  
Flow Cytometry ◽  
Cell Line ◽  
A549 Cell ◽  
Nuclear Translocation ◽  
A549 Cells ◽  
Inhibitory Effect ◽  
A549 Cell Line ◽  
Tnf Α ◽  
Lung Cancer A549 Cell

Our study examined for the inhibitory effect of ethanolic extract of Eleagnus Conferta Roxb leaves on TNF –α induced NF- kB nuclear translocation in lung cancer A549 cell line using flow cytometry. Apoptosis also studied to know about the antiproliferative and anticancer effects. However, our results revealed in apoptosis, Elaeagnus conferta Roxb leaves showed (33.54%) increased in proportion of cells. In the study of pre-treatment of A549 cells with Elaeagnus conferta Roxb leaves followed by TNF- α caused the increased proportion of cells (20.78%) at apoptosis induced cell death, which was statistically significant (p< 0.001). The untreated A549 cells had minimal NF-kB expression (0.25± 0.01%). However, the approach of A549 cells with Elaeagnus conferta Roxb had induced NF-kB production many fold (11.50± 1.05%). Therefore, we conclude our study was proved the impact of Elaeagnus conferta Roxb leaves inhibit the cellular growth of NSCLC-A549 cell line and induces apoptosis. Hence, from our findings, we proved this plant has anticancer activity, further feasibly taken for drug formulation.

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.

Monoisopropylglutathione ester protects A549 cells from the cytotoxic effects of sulphur mustard

1997 ◽  
Vol 16 (11) ◽  
pp. 636-644 ◽  
Author(s):  
Christopher D Lindsay ◽  
Joy L Hambrook ◽  
Alison F Lailey
Keyword(s):  
Cell Viability ◽  
Cell Cultures ◽  
A549 Cell ◽  
High Performance ◽  
Gentian Violet ◽  
A549 Cells ◽  
Rapid Onset ◽  
Neutral Red ◽  
Biochemical Basis ◽  
Sulphur Mustard

1 The A549 cell line was used to assess the toxicity of sulphur mustard (HD), using gentian violet (GV) and neutral red (NR) dyes as indicators of cell viability. It was found that exposure to concentrations in excess of 40 ?M HD resulted in a rapid onset of toxicity. 2 The ability of monoisopropylglutathione ester (MIPE) to protect A549 cells against the effects of a 100 ?M challenge dose ofHD was determined using the NR and GV assays. It was found that MIPE (8 mM) could protect cells against the effects ofHD though MIPE had to be present at the time of HD challenge. Cultures protected with MIPE were two times more viable than HD exposed cells 48 h after HD challenge when using the GV and NR assays to assess viability. Observations by phase contrast microscopy of NR and GV stained cultures confirmed these findings. Addition of MIPE after previously exposing the A549 cultures to HD (for up to 5 min) maintained cell viability at 72% compared to 37% for unprotected cultures, after which time viability fell significantly so that at 10 min there was no difference in viability between the MIPE treated and untreated cultures. 3 Pretreating A549 cultures with MIPE for 1 h followed by its removal prior to HD challenge did not maintain cell viability. Treatment of cultures with HD for 1 h followed by addition of MIPE did not maintain the viability of the cultures, thus the window within which it was possible for MIPE to rescue cell cultures from the effects of HD was of short duration. 4 High performance liquid chromatography was used to determine the biochemical basis of the actions of MIPE. It was found that whilst intracellular levels of cysteine were increased up to 40-fold following treatment of A549 cell cultures with MIPE, levels of reduced glutathione did not rise. The lack of protection seen in cultures pretreated with MIPE for 1 h prior to HD exposure suggests that raising intracellular cysteine levels was not an effective strategy for protecting cells from the effects of HD. The protection observed is probably due to extra cellular inactivation of HD by MIPE.

scholarly journals α-Hederin Inhibits the Growth of Lung Cancer A549 Cells in vitro and in vivo by Increasing SIRT6 Dependent Glycolysis

2020 ◽  
Author(s):  
cong fang ◽  
Yahui Liu ◽  
Lanying Chen ◽  
Yingying Luo ◽  
Yaru Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Protein Expression ◽  
Glucose Uptake ◽  
A549 Cells ◽  
Lactate Production ◽  
Tumor Xenograft ◽  
Xenograft Mouse Model ◽  
Atp Generation

Abstract Background: α-hederin an effective component of Pulsatilla chinensis (Bunge) Regel, Studies showed that α-hederin exert many pharmacological activities, However, the effect of α-hederin on metabolism is still unclear. This study aimed to illuminate the role of α-hederin in glucose metabolism in lung cancer cells and investigate the molecular mechanism of α-hederin. Methods: CCK8 and colony formation assays were employed to assess the anti-proliferative effects induced by α-hederin. Glucose uptake, ATP generation, and reduced lactate production were measured using kits, and an A549 tumor xenograft mouse model of lung cancer was used to assess the in vivo antitumor effect of α-hederin (5, 10 mg/kg). Glycolytic-related key enzymes hexokinase 2 (HK2), glucose transporters 1 (GLUT1), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), monocarboxylate transporter (MCT4), c-Myc, Hypoxia inducible factor-1α (HIF-1α) and Sirtuin 6 (SIRT6) protein expression were detected by western blotting and immunohistochemical staining and SIRT6 inhibitors was verified in A549 cells. Results: Our results showed that cell proliferation was significantly inhibited by α-hederin in a dose-dependent manner and that α-hederin inhibited glucose uptake and ATP generation and reduced lactate production. Furthermore, α-hederin remarkably inhibited HK2, GLUT1, PKM2, LDHA, MCT4, c-Myc, HIF-1α and activated SIRT6 protein expression. Using inhibitors, we proved that α-hederin inhibits glycolysis by activating SIRT6. Moreover, a tumor xenograft mouse model of lung cancer further confirmed that α-hederin inhibits lung cancer growth via inhibiting glycolysis in vivo. Conclusions: α-hederin inhibits the growth of non-small cell lung cancer A549 cells by inhibiting glycolysis. The mechanism of glycolysis inhibition includes α-hederin activating the expression of the glycolytic related protein SIRT6.

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.

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