Development of Secondary Drug-Resistance and Radioresistance in a Human Neurogenic Sarcoma Xenografted onto Nude Mice

1992 ◽  
pp. 475-475
Author(s):  
W. Budach ◽  
V. Budach ◽  
M. Scheulen ◽  
M. Stuschke ◽  
P. Chaborski
Keyword(s):  
Drug Resistance ◽  
Nude Mice ◽  
Neurogenic Sarcoma

scholarly journals Cisplatin loaded multiwalled carbon nanotubes reverse drug resistance in NSCLC by inhibiting EMT

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuxin Qi ◽  
Wenping Yang ◽  
Shuang Liu ◽  
Fanjie Han ◽  
Haibin Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Carbon Nanotubes ◽  
Drug Resistance ◽  
Western Blot ◽  
Multiwalled Carbon Nanotubes ◽  
Cell Lines ◽  
Nude Mice ◽  
Expression Level ◽  
Multiwalled Carbon

Abstract Background Lung cancer is one of the important health threats worldwide, of which 5-year survival rate is less than 15%. Non-small-cell lung cancer (NSCLC) accounts for about 80% of all lung cancer with high metastasis and mortality. Methods Cisplatin loaded multiwalled carbon nanotubes (Pt-MWNTS) were synthesized and used to evaluate the anticancer effect in our study. The NSCLC cell lines A549 (cisplatin sensitive) and A549/DDP (cisplatin resistant) were used in our in vitro assays. MTT was used to determine Cancer cells viability and invasion were measured by MTT assay and Transwell assay, respectively. Apoptosis and epithelial-mesenchymal transition related marker proteins were measured by western blot. The in vivo anti-cancer effect of Pt-MWNTs were performed in male BALB/c nude mice (4-week old). Results Pt-MWNTS were synthesized and characterized by X-ray diffraction, Raman, FT-IR spectroscopy and scan electron microscopy. No significant cytotoxicity of MWNTS was detected in both A549/DDP and A549 cell lines. However, Pt-MWNTS showed a stronger inhibition effect on cell growth than free cisplatin, especially on A549/DDP. We found Pt-MWNTS showed higher intracellular accumulation of cisplatin in A549/DDP cells than free cisplatin and resulted in enhanced the percent of apoptotic cells. Western blot showed that application of Pt-MWNTS can significantly upregulate the expression level of Bax, Bim, Bid, Caspase-3 and Caspase-9 while downregulate the expression level of Bcl-2, compared with free cisplatin. Moreover, the expression level of mesenchymal markers like Vimentin and N-cadherin was more efficiently reduced by Pt-MWNTS treatment in A549/DDP cells than free cisplatin. In vivo study in nude mice proved that Pt-MWNTS more effectively inhibited tumorigenesis compared with cisplatin, although both of them had no significant effect on body weight. Conclusion Pt-MWNT reverses the drug resistance in the A549/DDP cell line, underlying its possibility of treating NSCLC with cisplatin resistance.

Mechanism Research of Reversal of Multidrug Resistance by the Application of 5-Bromotetrandrine and Magnetic Nanoparticle of Fe3O4 Combined with Daunorubicin in a Human-Nude Mice Xenograft Model

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5058-5058
Author(s):  
Bao-An Chen ◽  
Ya-nan Wu ◽  
Jian Cheng ◽  
Feng Gao ◽  
Wen-lin Xu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Nude Mice ◽  
Magnetic Nanoparticle ◽  
Multiple Drug Resistance ◽  
Xenograft Model ◽  
Tumor Formation ◽  
Multiple Drug ◽  
Inhibition Rate ◽  
Group 5

Abstract Objective: To establish the xenograft leukemia model with stable multiple drug resistance in nude mice; to investigate the reversal effect of 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR in vivo and to search for the possible reversal mechanisms. Methods: K562 and K562/A02 cells were respectively inoculated subcutaneously into back of athymic nude mice (1×107 cells/each) to establish the xenograft models. The tumor formation was evaluated by animal ultrasonic inspection. Tumors-bearing nude mice were assigned randomly to five groups which were treated with NS (A group); DNR 1mg/kg (B group); nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(C group): 5-BrTet 2.5mg/kg combined with DNR(D group); 5-Bromotetrandrine 2.5mg/kg and Magnetic nanoparticle of Fe3O4 combined with DNR 0.63mg/kg(E group) respectively. The incidence of tumor formation, growth characteristics, weight and volume of tumor were observed. The histopathologic examination of tumors and organs were detected. For resistant tumors, the protein levels of P-glycoprotein (P-gp) were detected by Western blot. Results: The tumor incidence was 100% in the nude mice inoculated with either K562 or K562/A02 cells. In 6 to 9 days,the tumors reached a volume of more than 1 00 mm3. In vivo, MTT assay showed K562/A02 tumor maintained the drug resistance. For K562 cells xenograft tumors, there were no apparent differences in tumor suppression effect between the B AC AD AE group. For K562/A02 cells xenograft tumors, 5-BrTet and Magnetic nanoparticle of Fe3O4 combined with DNR significantly suppressed growth of tumor: the inhibition rate was 62.76% while DNR alone be used, the inhibition rate was 3.68%. Pathologic examination of resistant tumors showed the tumors necrosis obviously in E group. Application of 5-BrTet and Magnetic nanoparticle of Fe3O4 inhibited the overexpression of P-gp. Conclusion: The xenograft leukemia nude mice model was maintain the multiple drug resistance. 5-Bromotetrandrine and Magnetic nanoparticle of Fe3O4 combined with DNR had a significant tumor-suppressing effect on MDR leukemia cells xenograft model.

scholarly journals Ophiopogonin B-inducing Pyroptosis Through Caspase-1/gsdmd Pathway Contributes to Alleviation of Paclitaxel Resistance in Lung Cancer Cells 

2020 ◽  
Author(s):  
Ziyu Cheng ◽  
Zhihui Li ◽  
Ling Gu ◽  
Liqiu Li ◽  
Qian Gao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Resistance ◽  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Nude Mice ◽  
Release Rate ◽  
Mitochondrial Membrane ◽  
A549 Cells ◽  
Caspase 1

Abstract Background: Drug resistance has become the main reason for the failure of tumor chemotherapy. In our previous study, ophiopogonin B (OP-B) has been verified to inhibit cell proliferation in numerous non-small cell lung cancer (NSCLC) cells. However, it is still unknown whether it can improve the drug resistance of lung cancer cells. Herein, we compared the inhibition effects of OP-B on NCI-H460, A549, A549/DDP and A549/PTX cells, and tried to find out the most sensible cell line to OP-B and the underlying reasons. Methods: The sensitivity of NCI-H460, A549, A549/DDP, and A549/PTX cells to OP-B was determined by CCK-8 assay, and the results were further verified in orthotopic tumor nude mice model and zebrafish tumor model. To identify pyroptosis in the cells, electron microscopy was used to observe cell morphology, flow cytometry was used to detect the mitochondrial membrane potential, and the LDH release rate was analyzed by microplate reader. Otherwise, immunofluorescence and immunohistochemical staining assay, western blot and qRT-PCR were used for detection of pyroptosis-correlated pathway.Results: In vitro, A549/DDP cell was verified to be most sensitive to OP-B than NCI-H460, A549, or A549/PTX cells. In vivo, OP-B inhibited the growth of A549/DDP orthotopic tumor more significantly than that of A549 both in nude mice and zebrafish models. Cell morphological feature, mitochondrial membrane potential, LDH release rate, production of IL-1β and expression of Caspase-1/GSDMD all showed that pyroptosis happened more significantly in A549/DDP cells than that in A549 cells after OP-B treatment.Conclusion: Though inducing more significantly pyroptosis by activating Caspase-1/GSDMD pathway, OP-B relieved DDP resistance of A549 cells.

scholarly journals Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaoqiong Luo ◽  
Jingxi Wei ◽  
Feng-lian Yang ◽  
Xiao-xia Pang ◽  
Feng Shi ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Drug Resistance ◽  
Cell Line ◽  
Nude Mice ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Cell Line Hela ◽  
Cervical Cancer Cells ◽  
Line Hela

Abstract Background There is growing evidence of the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). The objective was to discuss whether exosomal lncRNA HNF1A-AS1 impacted drug resistance in CC via binding to microRNA-34b (miR-34b) and regulating TUFT1 expression. Methods The expression of HNF1A-AS1 in normal cervical epithelial cells, cisplatin (DDP)-sensitive cell line (HeLa/S) and DDP-resistant cell line (HeLa/DDP) cells were detected. HeLa/S and HeLa/DDP cells were interfered with HNF1A-AS1 to determine IC50, proliferation, colony formation and apoptosis of CC cells. The exosomes were isolated and identified. Subcellular localization of HNF1A-AS1, expression of miR-34b and TUFT1 in receptor cells were also verified. The binding site between HNF1A-AS1 and miR-34b, together with miR-34b and TUFT1 were confirmed. Tumorigenic ability of cells in nude mice was also detected. Results HNF1A-AS1 was upregulated in DDP-resistant cell line HeLa/DDP. Silencing HNF1A-AS1 suppressed CC cell proliferation and promoted its apoptosis. HNF1A-AS1 was found to act as a competing endogenous RNA (ceRNA) of miR-34b to promote the expression of TUFT1. Exosomes shuttled HNF1A-AS1 promoted the proliferation and drug resistance of CC cells and inhibited their apoptosis by upregulating the expression of TUFT1 and downregulating miR-34b. Furthermore, suppressed exosomal HNF1A-AS1 in combination with DDP inhibited tumor growth in nude mice. Conclusion Our study provides evidence that CC-secreted exosomes carrying HNF1A-AS1 as a ceRNA of miR-34b to promote the expression of TUFT1, thereby promoting the DDP resistance in CC cells.

scholarly journals METTL3 promotes adriamycin resistance in MCF-7 breast cancer cells by accelerating pri-microRNA-221-3p maturation in a m6A-dependent manner

2021 ◽  
Author(s):  
Xiaoping Pan ◽  
Xiaolv Hong ◽  
Sumei Li ◽  
Ping Meng ◽  
Feng Xiao
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Nude Mice ◽  
Epigenetic Mechanism ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Cancer Resistance ◽  
Gene Assay ◽  
Resistance Protein ◽  
Mcf 7

AbstractBreast cancer (BC) is the most prevalent malignant neoplasm among women and is the fifth most common cause of cancer-associated death worldwide. Acquired chemoresistance driven by genetic and epigenetic alterations is a significant clinical challenge in treating BC. However, the mechanism of BC cell resistance to adriamycin (ADR) remains to be elucidated. In this study, we identified the methyltransferase-like 3/microRNA-221-3p/homeodomain-interacting protein kinase 2/Che-1 (METTL3/miR-221-3p/HIPK2/Che-1) axis as a novel signaling event that may be responsible for resistance of BC cells to ADR. A dual-luciferase reporter gene assay was employed to test the presence of miR-221-3p binding sites in the 3′UTR of HIPK2. Drug resistance was evaluated by immunoblotting multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP). Cultured ADR-resistant MCF-7 cells were assayed for their half maximal inhibitory concentration (IC50) values and apoptosis using an MTT assay and Annexin V-FITC/PI-labeled flow cytometry, and the cells were then xenografted into nude mice. METTL3 knockdown was shown to reduce the expression of miR-221-3p by reducing pri-miR-221-3p m6A mRNA methylation, thereby reducing the IC50 value of ADR-resistant MCF-7 cells, reducing the expression of MDR1 and BCRP, and inducing apoptosis. Mechanistically, miR-221-3p was demonstrated to negatively regulate HIPK2 and upregulate its direct target Che-1, thus leading to enhanced drug resistance in ADR-resistant MCF-7 cells. In vitro results were reproduced in nude mice xenografted with ADR-resistant MCF-7 cells. Our work elucidates an epigenetic mechanism of acquired chemoresistance in BC, in support of the METTL3/miR-221-3p/HIPK2/Che-1 axis as a therapeutic target for the improvement of chemotherapy.

Ultrastructure of NPC/HK1 cells heterotransplanted in athymic nude mice

1982 ◽  
Vol 40 ◽  
pp. 236-237
Author(s):  
E.C. Chew ◽  
C.L. Li ◽  
D.P. Huang ◽  
H.C. Ho ◽  
L.S. Mak ◽  
...  
Keyword(s):  
Cell Line ◽  
Nude Mice ◽  
Biopsy Specimen ◽  
Epithelial Cell Line ◽  
Present Communication ◽  
Recurrent Tumour ◽  
Athymic Nude Mice ◽  
Cell Line Establishment ◽  
Fine Structures ◽  
Well Differentiated

An epithelial cell line, NPC/HK1, has recently been established from a biopsy specimen of a recurrent tumour of the nasopharynx which was histologically diagnosed as a moderately to well differentiated squamous cell carcinoma. A definite decrease in the amount of tonofilaments and desmosomes in the NPC/HK1 cells during the cell line establishment was observed. The present communication reports on the fine structures of the NPC/HK1 cells heterotraneplanted in athymic nude mice.

Sequential detection of mRNA for the chemokine IL-8 and macrophages (F4/80) in human melanoma

1995 ◽  
Vol 53 ◽  
pp. 1008-1009
Author(s):  
C.D. Bucana ◽  
R. Sanchez ◽  
R. Singh ◽  
I.J. Fidler
Keyword(s):  
Tumor Cells ◽  
Nude Mice ◽  
Constitutive Expression ◽  
Metastatic Potential ◽  
Melanoma Cells ◽  
Human Melanoma ◽  
Angiogenic Factor ◽  
Infiltrating Cells ◽  
Immunoperoxidase Assay ◽  
Multifunctional Cytokine

The purpose of this study was to demonstrate by ISH the presence of IL-8 mRNA, and by immunohistochemistry (IHC) the presence of the chemokine IL-8 and the distribution of infiltrating macrophages in subcutaneous melanomas in the same tumor. IL-8 is a multifunctional cytokine produced by melanoma cells, activated macrophages and monocytes and it has been shown to be a growth and angiogenic factor for tumor cells. More recently it was shown that constitutive expression of IL-8 correlated directly with metastatic potential of human melanoma cells in nude mice. IL-8 content of a solid tumor as determined by Western blot analysis does not take into account the contribution of macrophages. Previous studies showed that murine tumors contain many infiltrating cells interspersed among tumor cells whereas human tumors growing in nude mice exhibit macrophages at the periphery or between tumor islands. In this study we demonstrate the expression of IL-8 and the distribution of macrophages by immunoperoxidase assay and IL-8 mRNA by ISH.

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