scholarly journals Doxorubicin and siRNA co-delivery System Based on Carbon Dots Inhibits Chemoresistance of Lung Cancer Through MRP1

2021 ◽  
Author(s):  
Luo Hui ◽  
Tang Kexin ◽  
Lin Xi ◽  
Huang Yongquan ◽  
Yu Ting ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Delivery System ◽  
Carbon Dots ◽  
Raw Materials ◽  
Unmet Need ◽  
Metastatic Potential ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Clinical Practices ◽  
Surface Modified

Abstract BackgroundAcquired resistance against chemotherapeutic drugs hinders the clinical efficacy of treatments in lung cancer. To circumvent the developed resistance, we aim to target critical signaling molecules related with chemoresistance through co-delivering siRNA and chemotherapeutics. The co-delivery strategy may address the unmet need to efficiently counteracting the multidrug resistance in treating lung cancer. MethodsA co-delivery nanosystem that could carry siRNA and DOX simultaneously has been studied in this work. The co-delivery is based on carbon dots was surface-modified with poly-ethylenimine (PEI), and loaded the siMRP1 and chemotherapeutics on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI were raw materials and passivator during the reaction process that makes CD exhibit excellent optical property.ResultsThe CD-PEI was capable of loading and delivering siMRP1 and DOX to tumor and release synchronously in cells by acid-triggered manner.The expression of MRP1 in A549 and A549/ADM cells were successfully knocked down by siRNA. The silencing of MRP1 by co-delivery system could increase DOX accumulation and significantly enhance the inhibitory effect of cell viability. Moreover, the co-delivery system enhances the inhibitory effect of metastatic potential elicited by doxorubicin in A549 and A549/ADM cells.ConclusionBy suppressing MRP1, the co-delivery system can obviously increase the drug cellular accumulation and inhibit the cell proliferation, migration and invasion of lung cancer, implying its potential application to overcome chemoresistance and enhance therapeutic efficiency in clinical practices.

Doxorubicin and siRNA Co-Delivery System Based on Carbon Dots Inhibits Chemoresistance of Lung Cancer

2021 ◽  
Author(s):  
Hui Luo ◽  
Kexin Tang ◽  
Kaichen Huang ◽  
Xi Lin ◽  
Chaoming Mei ◽  
...  
Keyword(s):  
Delivery System ◽  
Carbon Dots ◽  
Laser Scanning ◽  
Raw Materials ◽  
Metastatic Potential ◽  
Laser Scanning Microscopy ◽  
Migration And Invasion ◽  
Confocal Laser ◽  
Clinical Practices ◽  
Anti Cancer

Abstract BackgroundThe resistance to the anti-cancer agent limits the chemotherapy effect in the cancer therapy. Tumor easily develops resistance to anti-cancer drugs leading to decreased therapy efficiency of chemotherapies. Targeting signaling molecules related with chemoresistance through strategy of co-delivery siRNA and chemotherapeutics may overcome the multidrug resistance to chemotherapy. A co-delivery nanosystem that could carry siRNA and DOX simultaneously has been studied in this work. ResultsThe co-delivery is based on carbon dots was surface-modified with poly-ethylenimine (PEI), and loaded the siMRP1 and chemotherapeutics by electronstatic interactions on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI were raw materials and passivator during the reaction process that makes CD exhibit excellent optical property and the capability of loading siRNA. The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumor and release synchronously in cell by pH-triggered manner using flow cytometry and confocal laser scanning microscopy analysis. MRP1 was successfully knocked down by siRNA. The silencing of MRP1 by co-delivery system could increase DOX accumulation and significantly enhance the inhibitory effect of metastatic potential elicited by doxorubicin in A549 and A549/ADM cells.ConclusionThe co-delivery systems effectively loaded and released siRNA and DOX agents to the targeted tumor, overcoming the resistant to chemotherapy. By suppressing MRP1, CD-PEI-DOX-siMRP1 can obviously increase the drug intercellular accumulation and inhibit the cell proliferation, migration and invasion, implying its potential application in enhancing therapeutic efficiency in clinical practices.

Doxorubicin and siRNA Co-Delivery System Based on Carbon Dots Inhibits Chemoresistance of Lung Cancer

2021 ◽  
Author(s):  
Hui Luo ◽  
Kexin Tang ◽  
Kaichen Huang ◽  
Xi Lin ◽  
Chaoming Mei ◽  
...  
Keyword(s):  
Delivery System ◽  
Carbon Dots ◽  
Laser Scanning ◽  
Raw Materials ◽  
Metastatic Potential ◽  
Laser Scanning Microscopy ◽  
Migration And Invasion ◽  
Confocal Laser ◽  
Clinical Practices ◽  
Anti Cancer

Abstract BackgroundThe resistance to the anti-cancer agent limits the chemotherapy effect in the cancer therapy. Tumor easily develops resistance to anti-cancer drugs leading to decreased therapy efficiency of chemotherapies. Targeting signaling molecules related with chemoresistance through strategy of co-delivery siRNA and chemotherapeutics may overcome the multidrug resistance to chemotherapy. A co-delivery nanosystem that could carry siRNA and DOX simultaneously has been studied in this work. ResultsThe co-delivery is based on carbon dots was surface-modified with poly-ethylenimine (PEI), and loaded the siMRP1 and chemotherapeutics by electronstatic interactions on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI were raw materials and passivator during the reaction process that makes CD exhibit excellent optical property and the capability of loading siRNA. The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumor and release synchronously in cell by pH-triggered manner using flow cytometry and confocal laser scanning microscopy analysis. MRP1 was successfully knocked down by siRNA. The silencing of MRP1 by co-delivery system could increase DOX accumulation and significantly enhance the inhibitory effect of metastatic potential elicited by doxorubicin in A549 and A549/ADM cells.ConclusionThe co-delivery systems effectively loaded and released siRNA and DOX agents to the targeted tumor, overcoming the resistant to chemotherapy. By suppressing MRP1, CD-PEI-DOX-siMRP1 can obviously increase the drug intercellular accumulation and inhibit the cell proliferation, migration and invasion, implying its potential application in enhancing therapeutic efficiency in clinical practices.

scholarly journals Doxorubicin and siRNA Co-Delivery System Based on Carbon Dots Inhibits Metastasis of Lung Cancer by Attenuating Mrp1-Mediated Resistance

2020 ◽  
Author(s):  
Hui Luo ◽  
Kaichen Huang ◽  
Kexin Tang ◽  
Xi Lin ◽  
Chaoming Mei ◽  
...  
Keyword(s):  
Delivery System ◽  
Carbon Dots ◽  
Laser Scanning ◽  
Lung Tumor ◽  
Raw Materials ◽  
Bond Cleavage ◽  
Laser Scanning Microscopy ◽  
Migration And Invasion ◽  
Confocal Laser ◽  
Clinical Practices

Abstract BackgroundTumor easily develops resistance to anti-cancer drugs leading to decreased therapy efficiency of chemotherapies. Targeting signaling molecules related with chemoresistance through strategy of co-delivery siRNA and chemotherapeutics may overcome the multidrug resistance to chemotherapy. A co-delivery nanosystem that could carry siRNA and DOX simultaneously has been studied in this work. ResultsThe co-delivery is based on carbon dots was surface-modified with poly-ethylenimine (PEI), and loaded the siMRP1 and chemotherapeutics on the surface with pH-triggered drug release. The CD-PEI was synthesized by one-step microwave assisted method; the PEI were raw materials and passivator during the reaction process that makes CD exhibit excellent optical property. The CD-PEI was capable of loading and delivering siMRP1 and DOX to tumor and release synchronously in cell by acid-triggered manner, i.e. hydrazone bond cleavage and endosome/lysosome escape using flow cytometry and confocal laser scanning microscopy analysis. MRP1 was successfully knocked down by siRNA. The silencing of MRP1 by co-delivery system could increase DOX accumulation and significantly enhance the inhibitory effect of metastatic potential elicited by doxorubicin in A549 and A549/ADM cells.ConclusionThe co-delivery systems effectively loaded and released siRNA and DOX agents to the targeted lung tumor, overcoming the resistant to chemotherapy. By suppressing MRP1, CD-PEI-DOX-siMRP1 can obviously increase the drug intercellular accumulation and inhibit the cell proliferation, migration and invasion, implying its potential application in enhancing therapeutic efficiency in clinical practices.

scholarly journals Triptolide suppresses the growth and metastasis of non-small cell lung cancer by inhibiting β-catenin-mediated epithelial–mesenchymal transition

2021 ◽  
Author(s):  
Qiu-di Deng ◽  
Xue-ping Lei ◽  
Yi-hang Zhong ◽  
Min-shan Chen ◽  
Yuan-yu Ke ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Small Cell ◽  
Migration And Invasion ◽  
Ovarian Cancer Cells ◽  
Small Cell Lung ◽  
Mesenchymal Transition

AbstractNon-small cell lung cancer (NSCLC) is characterized by a high incidence of metastasis and poor survival. As epithelial–mesenchymal transition (EMT) is well recognized as a major factor initiating tumor metastasis, developing EMT inhibitor could be a feasible treatment for metastatic NSCLC. Recent studies show that triptolide isolated from Tripterygium wilfordii Hook F attenuated the migration and invasion of breast cancer, colon carcinoma, and ovarian cancer cells, and EMT played important roles in this process. In the present study we investigated the effect of triptolide on the migration and invasion of NSCLC cell lines. We showed that triptolide (0.5, 1.0, 2.0 nM) concentration-dependently inhibited the migration and invasion of NCI-H1299 cells. Triptolide treatment concentration-dependently suppressed EMT in NCI-H1299 cells, evidenced by significantly elevated E-cadherin expression and reduced expression of ZEB1, vimentin, and slug. Furthermore, triptolide treatment suppressed β-catenin expression in NCI-H1299 and NCI-H460 cells, overexpression of β-catenin antagonized triptolide-caused inhibition on EMT, whereas knockout of β-catenin enhanced the inhibitory effect of triptolide on EMT. Administration of triptolide (0.75, 1.5 mg/kg per day, ip, every 2 days) for 18 days in NCI-H1299 xenograft mice dose-dependently suppressed the tumor growth, restrained EMT, and decreased lung metastasis, as evidence by significantly decreased expression of mesenchymal markers, increased expression of epithelial markers as well as reduced number of pulmonary lung metastatic foci. These results demonstrate that triptolide suppresses NSCLC metastasis by targeting EMT via reducing β-catenin expression. Our study implies that triptolide may be developed as a potential agent for the therapy of NSCLC metastasis.

Antimigratory and antimetastatic effect of heparin-derived 4–18 unit oligosaccharides in a preclinical human melanoma metastasis model

2009 ◽  
Vol 102 (12) ◽  
pp. 1265-1273 ◽  
Author(s):  
István Kenessey ◽  
Erika Simon ◽  
Krisztina Futosi ◽  
Bíborka Bereczky ◽  
Andrea Kiss ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Migration ◽  
Metastatic Potential ◽  
Inhibitory Effect ◽  
Human Melanoma ◽  
Migration And Invasion ◽  
Melanoma Metastasis ◽  
Metastasis Model

SummaryHeparin and its derivatives have been shown to inhibit angiogenesis and metastasis formation. Accordingly, we investigated the effect of heparin fragments containing 4 to 22 monomers on human melanoma cell proliferation, migration and invasion in vitro as well as on the in vivo metastatic potential in a SCID mouse model. Only oligosaccharide dp18 had significant inhibitory effect on cell proliferation. In contrast, cell migration was inhibited by all oligosaccharides studied except dp8 and dp22. Anti CD44v3 antibody stimulated cell migration and invasion, and this effect could be attenuated by oligosaccharides dp4 and dp18. These fragments also inhibited the catalytic activity of myosin light chain phosphatase as well. Moreover, oligosaccharides dp4 and dp18 reduced the number of lung colonies formed in SCID mice intravenously injected with human melanoma cells, while dp22 proved to be ineffective in this respect.These studies revealed that fragments of heparin have an antimigratory and antimetastatic potential. These fragments lack the haemostatic effect of heparin, suggesting that they are potential specific antimetastatic agents in anticancer therapy.

scholarly journals The TCM Prescription Yi-Fei-Jie-Du-Tang Inhibit Invasive Migration and EMT of Lung Cancer Cells by Activating Autophagy

2021 ◽  
Author(s):  
Shanshan Wang ◽  
Zaichuan Wang ◽  
Yinqiu Wu ◽  
Chao Hou ◽  
Qingyin Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
A549 Cell ◽  
A549 Cells ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Tumor Bearing ◽  
Related Proteins

Abstract ObjectiveNon-small cell lung cancer (NSCLC) is a serious threat to people’s health. This study aims to assess the antitumor effect of Yi-Fei-Jie-Du-Tang (YFJDT) on NSCLC,which is an empirical formula from Professor Zhongying Zhou,and the underlying mechanisms.MethodsIn the present study, we determined the possible effects and potential mechanisms of YFJDT on an A549 cell tumor-bearing nude mice model and A549 cell model in vitro. Tumor-bearing mice were treated with YFJDT and tumors were measured during the experiment, and tumor tissues were collected at the end of the experiment to assess the levels of autophagy and epithelial-mesenchymal transition (EMT)-related proteins. ResultsThe results showed that YFJDT treatment reduced tumor volume and mass, increased the expression of the autophagy marker LC3 and inhibited EMT-related proteins compared to the model group.Cell survival was reduced in the YFJDT-treated group compared to the model group, and YFJDT also reduced the migration and invasion ability of A549 cells in a dose-dependent manner. Western blotting detected that YFJDT also upregulated FAT4 in tumor tissue and A549 cells and downregulated the expression of Vimentin. Meanwhile, apoptosis in both tissues and cells was greatly increased after YFJDT treatment. We further interfered with FAT4 expression in cells and found that the inhibitory effect of YFJDT on EMT was reversed, indicating that YFJDT affects EMT by regulating FAT4 expression. ConclusionTaken together, results of this study suggested that the inhibitory effect of YFJDT on EMT in lung cancer tumors is through upregulating FAT4, promoting autophagy and thus inhibiting EMT in cancer cells.

scholarly journals Isovitexin Suppresses Stemness of Lung Cancer Stem-Like Cells through Blockage of MnSOD/CaMKII/AMPK Signaling and Glycolysis Inhibition

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Fei Liu ◽  
Qing Yuan ◽  
Xiaocheng Cao ◽  
Jinlin Zhang ◽  
Jianguo Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Manganese Superoxide Dismutase ◽  
Inhibitory Effect ◽  
Soft Agar ◽  
Migration And Invasion ◽  
Self Renewal ◽  
Ampk Signaling ◽  
Signaling Axis

Background. Manganese superoxide dismutase (MnSOD) has been reported to promote stemness of lung cancer stem-like cells (LCSLCs) which had higher glycolytic rates compared with non-CSLCs. Isovitexin exhibited an inhibitory effect on the stemness of hepatocellular carcinoma cells. However, whether isovitexin could inhibit the promotion of stemness of LCSLCs mediated by MnSOD through glycolysis remains unclear. Objective. Our study was aimed at investigating whether isovitexin inhibits lung cancer stem-like cells (LCSLCs) through MnSOD signaling blockage and glycolysis suppression. Methods. Sphere formation and soft agar assays were conducted to determine self-renewal ability. The migration and invasion of LCSLCs were determined by wound healing and transwell assay. The glycolytic activity was assessed by determination of L-lactate metabolism rate. The influences of isovitexin on MnSOD, CaMKII, and AMPK activations as well as the metabolic shift to glycolysis were determined by manipulating MnSOD expression. Results. It was found that MnSOD and glycolysis enhanced simultaneously in LCSLCs compared with parental H460 cells. Overexpression of MnSOD activated CaMKII/AMPK signaling and glycolysis in LCSLCs with increased self-renewal, migration, invasion, and expression of stemness-associated markers in vitro and elevated carcinogenicity in vivo. Knockdown of MnSOD induced an inverse effect in LCSLCs. Isovitexin blocked MnSOD/CaMKII/AMPK signaling axis and suppressed glycolysis in LCSLCs, resulting in inhibition of stemness features in LCSLCs. The knockdown of MnSOD significantly augmented isovitexin-associated inhibition of CaMKII/AMPK signaling, glycolysis, and stemness in LCSLCs. However, the overexpression of MnSOD could attenuate the inhibition of isovitexin on LCSLCs. Importantly, isovitexin notably suppressed tumor growth in nude mice bearing LCSLCs by downregulation of MnSOD expression. Conclusion. MnSOD promotion of stemness of LCSLCs derived from H460 cell line is involved in the activation of the CaMKII/AMPK pathway and induction of glycolysis. Isovitexin-associated inhibition of stemness in LCSLCs is partly dependent on blockage of the MnSOD/CaMKII/AMPK signaling axis and glycolysis suppression.

scholarly journals Cyclic pentapeptide cRGDfK enhances the inhibitory effect of sunitinib on TGF-β1-induced epithelial-to-mesenchymal transition in human non-small cell lung cancer cells

2020 ◽  
Author(s):  
Kyeong-Yong Park ◽  
Jiyeon Kim
Keyword(s):  
Lung Cancer ◽  
Wnt Signaling ◽  
Cancer Cells ◽  
Human Lung ◽  
Inhibitory Effect ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Tgf Β1

AbstractIn human lung cancer progression, the EMT process is characterized by the transformation of cancer cells into invasive forms that migrate to other organs. Targeting to EMT-related molecules is emerging as a novel therapeutic approach for the prevention of lung cancer cell migration and invasion. Traf2- and Nck-interacting kinase (TNIK) has recently been considered as an anti-proliferative target molecule to regulate the Wnt signaling pathway in several types of cancer cells. In the present study, we evaluated the inhibitory effect of a tyrosine kinase inhibitor sunitinib and the integrin-αVβ3 targeted cyclic peptide (cRGDfK) on EMT in human lung cancer cells. Sunitinib strongly inhibited the TGF-β1-activated EMT through suppression of Wnt signaling, Smad and non-Smad signaling pathways. In addition, the cRGDfK also inhibited the expression of TGFβ1-induced mesenchymal marker genes and proteins. The anti-EMT effect of sunitinib was enhanced when cRGDfK was treated together. When sunitinib was treated with cRGDfK, the mRNA and protein expression levels of mesenchymal markers were decreased compared to the treatment with sunitinib alone. Co-treatment of cRGDfK has shown the potential to improve the efficacy of anticancer agents in combination with therapeutic agents that may be toxic at high concentrations. These results provide new and improved therapies for treating and preventing EMT-related disorders, such as lung fibrosis and cancer metastasis, and relapse.

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