Establishment of in vivo Skin, Liver and Lung Cancer Xenograft Models using NCI-H640 and HepG2 Cell Lines in Athymic Nude Mice

Planta Medica ◽  
2011 ◽  
Vol 77 (05) ◽  
Author(s):  
MS Abdel-Bakky ◽  
LA Walker ◽  
MK Ashfaq
Keyword(s):  
Lung Cancer ◽  
Hepg2 Cell ◽  
Cell Lines ◽  
Nude Mice ◽  
Athymic Nude Mice ◽  
Xenograft Models ◽  
Hepg2 Cell Lines

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.

scholarly journals ABCG2-overexpressing H460/MX20 cell xenografts in athymic nude mice maintained original biochemical and cytological characteristics

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Wei Zhang ◽  
Zhen Chen ◽  
Likun Chen ◽  
Fang Wang ◽  
Furong Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Nude Mice ◽  
Large Cell ◽  
Athymic Nude Mice ◽  
H460 Cell ◽  
Large Cell Lung Cancer ◽  
Cytological Characteristics

Abstract H460/MX20 are derived from large cell lung cancer H460 cell line and then transformed into ABCG2-overexpressing cells by mitoxantrone’s induction, which are widely used in study of multidrug resistance (MDR) in vitro. To establish and spread the model of H460/MX20 cell xenografts, we investigated whether cell biological characteristics and the MDR phenotype were maintained in vivo model. Our results demonstrated that the cell proliferation, cell cycle, and ABCG2 expression level in xH460/MX20 cells isolated from H460/MX20 cell xenografts were similar to H460/MX20 cells in vitro. Importantly, xH460/MX20 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan as H460/MX20 cells did. Furthermore, lapatinib, the inhibitor of ABCG2, potently reversed mitoxantrone- and topotecan-resistance of xH460/MX20 cells. Taken together, these results suggest that H460/MX20 cell xenografts in athymic nude mice still retain their original cytological characteristics and MDR phenotype. Thus, the H460/MX20 cell xenografts model could serve as a sound model in vivo for study on reversal MDR.

OSU-A9, An Indole-3-Carbinol Derivative, Induces Cytotoxicity In Acute Myeloid Leukemia Through Reactive Oxygen Species-Mediated Apoptosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2531-2531
Author(s):  
Li-Yuan Bai ◽  
Jing-Ru Weng ◽  
Chia-Yung Wu ◽  
Chang-Fang Chiu ◽  
Su-Peng Yeh ◽  
...  
Keyword(s):  
Cell Lines ◽  
Nude Mice ◽  
Myeloid Leukemia ◽  
Leukemia Cells ◽  
Parp Cleavage ◽  
Oxygen Species ◽  
Athymic Nude Mice ◽  
Primary Leukemia ◽  
Acute Myeloid

Abstract Introduction Indole-3-carbinol (I3C) is a broadly targeted phytochemical shown to prevent carcinogenesis in animal studies and to suppress the proliferation of cancer cells of human breast, colon, prostate, and endometrium. Here we aim to test the anticancer effect of OSU-A9, an I3C derivative with improved potency, in acute myeloid leukemia (AML). Materials and Methods The in vitro activity of OSU-A9 was evaluated in AML cell lines (HL-60 and THP-1) and primary leukemia cells from 18 AML patients. THP-1 xenograft tumors in athymic nude mice was used for in vivo study. Results OSU-A9 mediates cytotoxicity in AML cell lines and primary leukemia cells from AML patients in a dose-responsive manner. The IC50 at 24 h for 18 patients was 1.63 μM. Normal human bone marrow cells were much less sensitive to OSU-A9 with an IC50 at 24 h greater than 8 μM. OSU-A9 causes cytotoxicity dependent on caspase activation, as evidenced by caspase-3 and PARP cleavage, and induces autophagy but not autophagic cell death. Interestingly, pretreatment of AML cell lines and primary AML cells with N-acetylcysteine or glutathione rescues them from apoptosis (and concomitant PARP cleavage) and Akt hypophosphorylation, implicating a key role of reactive oxygen species (ROS) in OSU-A9-related cytotoxicity. To investigate the anti-leukemia effect of OSU-A9 in vivo, fifteen male athymic nude mice were xenografted with THP-1 cells. Briefly, the anticancer utility of OSU-A9 is extended in vivo as it, administered intraperitoneally, suppresses the growth of THP-1 xenograft tumors in athymic nude mice without obvious toxicity. For biomarker analysis in the THP-1 xenografts, protein extracts were obtained from the tumors and immunoblotted for Akt levels. The tumors from OSU-A9 treated mice exhibited down regulation of Akt phosphorylation compared with those from placebo-controlled mice. Conclusions This study shows that ROS-mediated apoptosis contributes to the anticancer activity of OSU-A9 in AML cell lines and primary AML cells, and thus should be considered in the future assessment of its translational value in AML therapy. Disclosures: No relevant conflicts of interest to declare.

Selenium Nanoparticles Induce Cytotoxicity and Apoptosis in Human Breast Cancer (MCF-7) and Liver (HepG2) Cell Lines

2020 ◽  
Vol 12 (3) ◽  
pp. 324-330
Author(s):  
Abdulsalam A. Alkhudhayri ◽  
Rizwan Wahab ◽  
Maqsood A. Siddiqui ◽  
Javed Ahmad
Keyword(s):  
Hepg2 Cell ◽  
Cell Lines ◽  
Selenium Nanoparticles ◽  
Model Systems ◽  
Mrna Levels ◽  
Hepg2 Cell Lines ◽  
Apoptotic Effects ◽  
Relative Differences ◽  
Mcf 7

This investigation was designed to assess the cytotoxic and apoptotic effects of selenium nanoparticles. It explored the cytotoxic effects of selenium nanoparticles in MCF-7 and HepG2 cell lines. The morphology of selenium nanoparticles was analyzed by transmission electron microscopy (TEM) to verify their size and crystalline properties. The selenium nanoparticles were almost spherical and cubic in shape and in size (∼20 nm). Selenium nanoparticles were tested for their cytotoxic activity in MCF-7 and HepG2 cell lines using MTT and NRU assays. We found relative differences in the vulnerability of both cell lines in their response to selenium nanoparticle-induced cytotoxicity. Specifically, MCF-7 cells exhibited greater vulnerability to exposure to selenium nanoparticles than HepG2 cells. Selenium nanoparticles exposure also induced higher mRNA levels of apoptosis related genes and caspase-3 enzyme activity. Overall, the present study provided the evidence of cytotoxicity induced by SeNPs via apoptotic gene expression in human cell lines. These results warrant further investigation into more precise mechanism(s) of selenium nanoparticles-induced cell death in in vivo model systems.

scholarly journals UBR-Box Containing Protein, UBR5, is Over-Expressed in Human Lung Adenocarcinoma and is a Potential Therapeutic Target

2020 ◽  
Author(s):  
Kumar Saurabh ◽  
Parag P Shah ◽  
Mark Doll ◽  
Leah J Siskind ◽  
Levi J. Beverly
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cell Lines ◽  
Nude Mice ◽  
Therapeutic Target ◽  
Human Lung ◽  
Human Patient ◽  
Adenocarcinoma Cell ◽  
Ubiquitination Pathway

Abstract Background:N-end rule ubiquitination pathway is known to be disrupted in many diseases, including cancer. UBR5, an E3 ubiquitin ligase, is mutated and/or overexpressed in human lung cancer cells suggesting its pathological role in cancer. Methods: We determined expression of UBR5 protein in multiple lung cancer cell lines and human patient samples.Using immunoprecipitation followed by mass spectrometry we determined the UBR5 interacting proteins. The impact of loss of UBR5 for lung adenocarcinoma cell lines was analyzed using cell viability, clonogenic assays and in vivo xenograft models in nude mice. Additional Western blot analysis was performed to assess the loss of UBR5 on downstream signaling. Statistical analysis was done by one-way ANOVA for in vitro studies and Wilcoxon paired t-test for tumor volumes in vivo.Results:We show variability of UBR5 expression levels in lung adenocarcinoma cell lines and in primary human patient samples.To gain better insight into the role that UBR5 may play in lung cancer progression we performed unbiased interactome analyses for UBR5. Dataindicate that UBR5 has a wide range of interacting protein partners that are known to be involved in critical cellular processes such as DNA damage, proliferation and cell cycle regulation. We have demonstrated thatshRNA-mediated lossof UBR5 decreases cell viabilityand clonogenic potential of lung adenocarcinoma cell lines.In addition, we founddecreased levels of activatedAKT signaling after the loss of UBR5 in lung adenocarcinoma cell lines using multiple means of UBR5 knockdown/knockout. Furthermore, we demonstrated that loss of UBR5 in lung adenocarcinoma cells results in significant reduction of tumor volume in nude mice. Conclusions:These findings demonstrate that deregulation of the N-end rule ubiquitination pathway plays a crucial role in the etiology of some human cancers, and blocking this pathway via UBR5-specific inhibitors, may represent a unique therapeutic target for human cancers.

scholarly journals Tumorigenicity and Validity of Fluorescence Labelled Mesenchymal and Epithelial Human Oral Cancer Cell Lines in Nude Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Wei Xin Cai ◽  
Li Wu Zheng ◽  
Li Ma ◽  
Hong Zhang Huang ◽  
Ru Qing Yu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Nude Mice ◽  
Tongue Cancer ◽  
Cancer Cell Lines ◽  
Fluorescent Imaging ◽  
Cell Phenotype ◽  
Human Tongue

Tumorigenicity and metastatic activity can be visually monitored in cancer cells that were labelled with stable fluorescence. The aim was to establish and validate local and distant spread of subcutaneously previously injected fluorescence transduced human tongue cancer cell lines of epithelial and mesenchymal phenotype in nude mice. A total of 32 four-week-old male athymic Balb/c nude mice were randomly allocated into 4 groups (n=8). A single dose of 0.3 mL PBS containing 1 × 107 of four different cancer cell-lines (UM1, UM1-GFP, UM2, and UM2-RFP) was injected subcutaneously into the right side of their posterolateral back. Validity assessment of the labelled cancer cells’ tumorigenicity was assessed by physical examination, imaging, and histology four weeks after the injection. The tumor take rate of cancer cells was similar in animals injected with either parental or transduced cancer cells. Transduced cancer cells in mice were easily detectable in vivo and after cryosection using fluorescent imaging. UM1 cells showed increased tumor take rate and mean tumor volume, presenting with disorganized histopathological patterns. Fluorescence labelled epithelial and mesenchymal human tongue cancer cell lines do not change in tumorigenicity or cell phenotype after injection in vivo.

scholarly journals Therapeutic evaluation of palbociclib and its compatibility with other chemotherapies for primary and recurrent nasopharyngeal carcinoma

2020 ◽  
Author(s):  
zhichao xue ◽  
Vivian Wai Yan Lui ◽  
Yongshu Li ◽  
Jia Lin ◽  
Chanping You ◽  
...  
Keyword(s):  
Cell Death ◽  
Nasopharyngeal Carcinoma ◽  
Cell Lines ◽  
Chemotherapeutic Drugs ◽  
Induce Cell Cycle Arrest ◽  
Ki 67 ◽  
Concurrent Treatment ◽  
Xenograft Models

Abstract Background: Recent genomic analyses revealed that druggable molecule targets were detectable in approximately 6% of patients with nasopharyngeal carcinoma (NPC). However, a dependency on dysregulated CDK4/6–cyclinD1 pathway signaling is an essential event in the pathogenesis of NPC. In this study, we aimed to evaluate the therapeutic efficacy of a specific CDK4/6 inhibitor, palbociclib, and its compatibility with other chemotherapeutic drugs for the treatment of NPC by using newly established xenograft models and cell lines derived from primary, recurrent, and metastatic NPC. Methods: We evaluated the efficacies of palbociclib monotherapy and concurrent treatment with palbociclib and cisplatin or suberanilohydroxamic acid (SAHA) in NPC cell lines and xenograft models. RNA sequencing was then used to profile the drug response–related pathways. Palbociclib-resistant NPC cell lines were established to determine the potential use of cisplatin as a second-line treatment after the development of palbociclib resistance. We further examined the efficacy of palbociclib treatment against cisplatin-resistant NPC cells. Results: In NPC cells, palbociclib monotherapy was confirmed to induce cell cycle arrest in the G1 phase in vitro . Palbociclib monotherapy also had significant inhibitory effects in all six tested NPC tumor models in vivo , as indicated by substantial reductions in the total tumor volumes and in Ki-67 proliferation marker expression. In NPC cells, concurrent palbociclib treatment mitigated the cytotoxic effect of cisplatin in vitro . Notably, concurrent treatment with palbociclib and SAHA synergistically promoted NPC cell death both in vitro and in vivo . This combination also further inhibited tumor growth by inducing autophagy-associated cell death. NPC cell lines with induced palbociclib or cisplatin resistance remained sensitive to treatment with cisplatin or palbociclib, respectively. Conclusions: Our study findings provide essential support for the use of palbociclib as an alternative therapy for NPC and increase awareness of the effective timing of palbociclib administration with other chemotherapeutic drugs. Our results provide a foundation for the design of first-in-human clinical trials of palbociclib regimens in patients with NPC.

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