Targeted Photodynamic Therapy (PDT) of Lung Cancer with Biotinylated Silicon (IV) Phthalocyanine.

Background: Lung cancer is the leading cause of cancer-associated mortality in the world. Traditional cancer therapies prolong life expectancy of patients but often suffer from adverse reactions. Photodynamic therapy (PDT) has been recommended as a treatment option for lung cancer in several countries, due to its non-invasive procedures, high selectivity and weak side effects. Objective: We have designed and synthesized a biotin receptor-targeted silicon phthalocyanine (IV) (compound 1) which showed good therapeutic effect on biotin receptor-positive tumors. Since the overexpression of biotin receptor (BR) is also present in human lung cancer cells (A549), we explored the therapeutic properties of compound 1 on A549 xenograft tumor models. Method: The selectivity of compound 1 toward A549 cells was studied with fluorescence microscope and IVIS Spectrum Imaging System. The cytotoxicity was measured using MTT assay. In vivo anti-tumor activity was investigated on the nude mice bearing A549 xenografts. Results: In vitro assays proved that compound 1 could selectively accumulate in A549 cells via the BR-mediated internalization. In vivo imaging and distribution experiments showed that compound 1 could selectively accumulate in tumor tissues of tumor-bearing mice. After 16 days of the treatment, the volumes of tumor in PDT group were obviously smaller than that in other groups. Conclusion: This study demonstrates that compound 1 is a promising photosensitizer and has broad application prospects in clinical PDT of lung cancers.

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Molecular Role of EGFR-MAPK Pathway in Patchouli Alcohol-Induced Apoptosis and Cell Cycle Arrest on A549 CellsIn VitroandIn Vivo

BioMed Research International ◽

10.1155/2016/4567580 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 4

Author(s):

XinGang Lu ◽

Liu Yang ◽

ChengHua Lu ◽

ZhenYu Xu ◽

HongFu Qiu ◽

...

Keyword(s):

Lung Cancer ◽

Mapk Pathway ◽

A549 Cells ◽

Human Lung Cancer ◽

Activity Measurement ◽

Cover Glass ◽

Patchouli Alcohol ◽

Pogostemon Cablin

Nowadays, chemotherapy is still the main effective treatment for cancer. Herb prescriptions containingPogostemon cablin Benth(also known as “Guang-Huo-Xiang”) have been widely used in Chinese medicine today. In our research, we found that patchouli alcohol, a compound isolated from the oil ofPogostemon cablin Benth, exerted antitumor ability against human lung cancer A549 cells ability bothin vitroandin vivo. MTT assay was used to assess cell viability. Hoechst 33342 staining and TUNEL cover glass staining provided the visual evidence of apoptosis. Caspase activity measurement showed that patchouli alcohol activated caspase 9 and caspase 3 of mitochondria-mediated apoptosis. Consistently, patchouli alcohol inhibited the xenograft tumorin vivo. Further investigation of the underlying molecular mechanism showed that MAPK and EGFR pathway might contribute to the antitumor effect of patchouli alcohol. Our study proved that patchouli alcohol might be able to serve as a novel antitumor compound in the clinical treatment of lung cancer.

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In vitro and in vivo studies of a novel potential anticancer agent of isochaihulactone on human lung cancer A549 cells

Biochemical Pharmacology ◽

10.1016/j.bcp.2006.04.031 ◽

2006 ◽

Vol 72 (3) ◽

pp. 308-319 ◽

Cited By ~ 58

Author(s):

Yi-Lin Chen ◽

Shinn-Zong Lin ◽

Jang-Yang Chang ◽

Yeung-Leung Cheng ◽

Nu-Man Tsai ◽

...

Keyword(s):

Lung Cancer ◽

Anticancer Agent ◽

Human Lung ◽

A549 Cells ◽

In Vivo Studies ◽

Human Lung Cancer

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Discovery of new fluorescent thiazole–pyrazoline derivatives as autophagy inducers by inhibiting mTOR activity in A549 human lung cancer cells

Cell Death and Disease ◽

10.1038/s41419-020-02746-w ◽

2020 ◽

Vol 11 (7) ◽

Cited By ~ 2

Author(s):

ZhaoMin Lin ◽

ZhaoYang Wang ◽

XueWen Zhou ◽

Ming Zhang ◽

DongFang Gao ◽

...

Keyword(s):

Lung Cancer ◽

Human Lung ◽

Vascular Endothelial Cell ◽

Chorioallantoic Membrane ◽

A549 Cells ◽

Biological Evaluation ◽

Human Lung Cancer ◽

Dependent Manner

AbstractA series of fluorescent thiazole–pyrazoline derivatives was synthesized and their structures were characterized by 1H NMR, 13C NMR, and HRMS. Biological evaluation demonstrated that these compounds could effectively inhibit the growth of human non-small cell lung cancer (NSCLC) A549 cells in a dose- and time-dependent manner in vitro and inhibit tumor growth in vivo. The structure–activity relationship (SAR) of the compounds was analyzed. Further mechanism research revealed they could induce autophagy and cell cycle arrest while had no influence on cell necrosis. Compound 5e inhibited the activity of mTOR via FKBP12, which could be reversed by 3BDO, an mTOR activator and autophagy inhibitor. Compound 5e inhibited growth, promoted autophagy of A549 cells in vivo. Moreover, compound 5e showed good selectivity with no influence on normal vascular endothelial cell growth and the normal chick embryo chorioallantoic membrane (CAM) capillary formation. Therefore, our research provides potential lead compounds for the development of new anticancer drugs against human lung cancer.

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MSCs-engineered biomimetic PMAA nanomedicines for multiple bioimaging-guided and photothermal-enhanced radiotherapy of NSCLC

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00823-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yipengchen Yin ◽

Yongjing Li ◽

Sheng Wang ◽

Ziliang Dong ◽

Chao Liang ◽

...

Keyword(s):

Lung Cancer ◽

Cell Membranes ◽

Imaging System ◽

Fluorescence Signal ◽

Bimodal Imaging ◽

Red Blood Cell Membranes ◽

Magnetic Resonance Imaging Mri ◽

Tumor Accumulation

Abstract Background The recently developed biomimetic strategy is one of the mostly effective strategies for improving the theranostic efficacy of diverse nanomedicines, because nanoparticles coated with cell membranes can disguise as “self”, evade the surveillance of the immune system, and accumulate to the tumor sites actively. Results Herein, we utilized mesenchymal stem cell memabranes (MSCs) to coat polymethacrylic acid (PMAA) nanoparticles loaded with Fe(III) and cypate—an derivative of indocyanine green to fabricate Cyp-PMAA-Fe@MSCs, which featured high stability, desirable tumor-accumulation and intriguing photothermal conversion efficiency both in vitro and in vivo for the treatment of lung cancer. After intravenous administration of Cyp-PMAA-Fe@MSCs and Cyp-PMAA-Fe@RBCs (RBCs, red blood cell membranes) separately into tumor-bearing mice, the fluorescence signal in the MSCs group was 21% stronger than that in the RBCs group at the tumor sites in an in vivo fluorescence imaging system. Correspondingly, the T1-weighted magnetic resonance imaging (MRI) signal at the tumor site decreased 30% after intravenous injection of Cyp-PMAA-Fe@MSCs. Importantly, the constructed Cyp-PMAA-Fe@MSCs exhibited strong photothermal hyperthermia effect both in vitro and in vivo when exposed to 808 nm laser irradiation, thus it could be used for photothermal therapy. Furthermore, tumors on mice treated with phototermal therapy and radiotherapy shrank 32% more than those treated with only radiotherapy. Conclusions These results proved that Cyp-PMAA-Fe@MSCs could realize fluorescence/MRI bimodal imaging, while be used in phototermal-therapy-enhanced radiotherapy, providing desirable nanoplatforms for tumor diagnosis and precise treatment of non-small cell lung cancer.

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POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01476-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ronggang Luo ◽

Yi Zhuo ◽

Quan Du ◽

Rendong Xiao

Keyword(s):

Lung Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Cancer Progression ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

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α-Hederin inhibits the growth of lung cancer A549 cells in vitro and in vivo by decreasing SIRT6 dependent glycolysis

Pharmaceutical Biology ◽

10.1080/13880209.2020.1862250 ◽

2020 ◽

Vol 59 (1) ◽

pp. 11-20

Author(s):

Cong Fang ◽

Yahui Liu ◽

Lanying Chen ◽

Yingying Luo ◽

Yaru Cui ◽

...

Keyword(s):

Lung Cancer ◽

A549 Cells

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In vitro photodynamic therapy of human lung cancer: Investigation of dose-rate effects

Lung Cancer ◽

10.1016/0169-5002(90)90378-y ◽

1990 ◽

Vol 6 (1-2) ◽

pp. 63

Author(s):

W Matthews ◽

J Cook ◽

JB Mitchell ◽

RR Perry ◽

S Evans ◽

...

Keyword(s):

Lung Cancer ◽

Photodynamic Therapy ◽

Dose Rate ◽

Human Lung ◽

Human Lung Cancer ◽

Dose Rate Effects ◽

Rate Effects

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Functional Gene Knockout of NRF2 Increases Chemosensitivity of Human Lung Cancer A549 Cells In Vitro and in a Xenograft Mouse Model

Molecular Therapy — Oncolytics ◽

10.1016/j.omto.2018.10.002 ◽

2018 ◽

Vol 11 ◽

pp. 75-89 ◽

Cited By ~ 11

Author(s):

Pawel Bialk ◽

Yichen Wang ◽

Kelly Banas ◽

Eric B. Kmiec

Keyword(s):

Lung Cancer ◽

Mouse Model ◽

Human Lung ◽

Gene Knockout ◽

A549 Cells ◽

Functional Gene ◽

Human Lung Cancer ◽

Xenograft Mouse Model

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Metabolic breakdown of non-small cell lung cancers by mitochondrial HSPD1 targeting

10.1101/2021.03.09.434573 ◽

2021 ◽

Author(s):

Beatrice Parma ◽

Vignesh Ramesh ◽

Paradesi Naidu Gollavilli ◽

Aarif Siddiqui ◽

Luisa Pinna ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Progression ◽

Therapeutic Potential ◽

Small Cell ◽

Small Cell Lung ◽

Lung Cancers ◽

Metabolism Enzymes ◽

Shock Proteins

ABSTRACTThe identification of novel targets is of paramount importance to develop more effective drugs and improve the treatment of non-small cell lung cancer (NSCLC), the leading cause of cancer-related deaths worldwide. Since cells alter their metabolic rewiring during tumorigenesis and along cancer progression, targeting key metabolic players and metabolism-associated proteins represents a valuable approach with a high therapeutic potential. Metabolic fitness relies on the functionality of heat shock proteins (HSPs), molecular chaperones that facilitate the correct folding of metabolism enzymes and their assembly in macromolecular structures. Here, we show HSPD1 (HSP60) as a survival gene ubiquitously expressed in NSCLC and associated with poor patients’ prognosis. HSPD1 knockdown or its chemical disruption by the small molecule KHS101 induces a drastic breakdown of oxidative phosphorylation, and suppresses cell proliferation both in vitro and in vivo. By combining drug profiling with transcriptomics and through a whole-genome CRISPR/Cas9 screen, we demonstrate that HSPD1-targeted anti-cancer effects are dependent on OXPHOS and validated molecular determinants of KHS101 sensitivity, in particular, the creatine-transporter SLC6A8 and the subunit of the cytochrome c oxidase complex COX5B. These results highlight mitochondrial metabolism as an attractive target and HSPD1 as a potential theranostic marker for developing therapies to combat NCSLC.SignificanceHSPD1 elimination or disruption interferes with NSCLC metabolic activity causing a strong OXPHOS-dependent energetic breakdown, which the cancer cells fail to overcome, highlighting HSPD1 as a potential theranostic marker for improving lung cancer therapy.

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