In vivo efficacy and enhanced tumour accumulation of liposomal vinorelbine (TLC178) in human sarcoma xenograft mice model

Background: We have previously shown that 3-Deazaneplanocin A (DZNep) induces apoptosis in chondrosarcomas. Herein, we tested whether the combination of this epigenetic drug to a standard anticancer therapy may enhance the response to each drug in these bone tumors. Methods: Two chondrosarcoma cell lines (SW1353 and JJ012) were cultured in the presence of DZNep and/or cisplatin. Cell growth was evaluated by counting viable cells, and apoptosis was determined by Apo2.7 expression by flow cytometry. In vivo, the antitumoral effect of the DZNep/cisplatin combination was assessed through measurements of tumor volume of JJ012 xenografts in nude mice. Results: In vitro, the DZNep/cisplatin combination reduced cell survival and increased apoptosis compared to each drug alone in chondrosarcomas, but not in normal cells (chondrocytes). This enhancement of the antitumoral effect of the DZNep/cisplatin combination required a priming incubation with DZNep before the co-treatment with DZNep/cisplatin. Furthermore, in the chondrosarcoma xenograft mice model, the combination of both drugs more strongly reduced tumor growth and induced more apoptosis in tumoral cells than each of the drugs alone. Conclusion: Our results show that DZNep exposure can presensitize chondrosarcoma cells to a standard anticancer drug, emphasizing the promising clinical utilities of epigenetic-chemotherapeutic drug combinations in the future treatment of chondrosarcomas.

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Importance of the fatty acid chain length on in vitro and in vivo anticancer activity of fattigation-platform albumin nanoparticles in human colorectal cancer xenograft mice model

Journal of Controlled Release ◽

10.1016/j.jconrel.2020.05.001 ◽

2020 ◽

Vol 324 ◽

pp. 55-68

Author(s):

Chulhun Park ◽

Namhyun Baek ◽

Raimar Loebenberg ◽

Beom-Jin Lee

Keyword(s):

Colorectal Cancer ◽

Fatty Acid ◽

Mice Model ◽

Human Colorectal Cancer ◽

Albumin Nanoparticles ◽

Fatty Acid Chain ◽

Xenograft Mice Model ◽

Xenograft Mice

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The Deubiquitinating Enzyme Inhibitor PR-619 Enhances the Cytotoxicity of Cisplatin via the Suppression of Anti-Apoptotic Bcl-2 Protein: In Vitro and In Vivo Study

Cells ◽

10.3390/cells8101268 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1268 ◽

Cited By ~ 5

Author(s):

Kuan-Lin Kuo ◽

Shing-Hwa Liu ◽

Wei-Chou Lin ◽

Po-Ming Chow ◽

Yu-Wei Chang ◽

...

Keyword(s):

Antitumor Effect ◽

Enzyme Inhibitor ◽

Critical Role ◽

Deubiquitinating Enzymes ◽

Mice Model ◽

Bladder Urothelial Carcinoma ◽

Xenograft Mice Model ◽

Xenograft Mice

After chemotherapy for the treatment of metastatic bladder urothelial carcinoma (UC), most patients inevitably encounter drug resistance and resultant treatment failure. Deubiquitinating enzymes (DUBs) remove ubiquitin from target proteins and play a critical role in maintaining protein homeostasis. This study investigated the antitumor effect of PR-619, a DUBs inhibitor, in combination with cisplatin, for bladder UC treatment. Our results showed that PR-619 effectively induced dose- and time-dependent cytotoxicity, apoptosis, and ER-stress related apoptosis in human UC (T24 and BFTC-905) cells. Additionally, co-treatment of PR-619 with cisplatin potentiated cisplatin-induced cytotoxicity in UC cells and was accompanied by the concurrent suppression of Bcl-2. We also proved that Bcl-2 overexpression is related to the chemo-resistant status in patients with metastatic UC by immunohistochemistry (IHC) staining. In a xenograft mice model, we confirmed that PR-619 enhanced the antitumor effect of cisplatin on cisplatin-naïve and cisplatin-resistant UCs. Our results demonstrated that PR-619 effectively enhanced the cisplatin-induced antitumor effect via concurrent suppression of the Bcl-2 level. These findings provide promising insight for developing a therapeutic strategy for UC treatment.

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Polyphenolic Fraction Obtained From Thalassia testudinum Marine Plant and Thalassiolin B Exert Cytotoxic Effects in Colorectal Cancer Cells and Arrest Tumor Progression in a Xenograft Mouse Model

Frontiers in Pharmacology ◽

10.3389/fphar.2020.592985 ◽

2020 ◽

Vol 11 ◽

Author(s):

Livan Delgado-Roche ◽

Kethia González ◽

Fernando Mesta ◽

Beatriz Couder ◽

Zaira Tavarez ◽

...

Keyword(s):

Colorectal Cancer ◽

Antitumor Activity ◽

Thalassia Testudinum ◽

Ros Generation ◽

Mice Model ◽

Marine Plant ◽

Colorectal Cancer Cells ◽

Xenograft Mice Model ◽

Xenograft Mice

Marine plants are important sources of pharmacologically active metabolites. The aim of the present work was to evaluate the cytotoxic and antitumor activity of a polyphenolic fraction obtained from Thalassia testudinum marine plant and thalassiolin B in human colorectal cancer cells. Human cancer cell lines, including HCT15, HCT116, SW260, and HT29 were treated with tested products for cytotoxicity evaluation by crystal violet assay. The potential proapoptotic effect of these natural products was assessed by flow cytometry in HCT15 cells at 48 h using Annexin V-FITC/propidium iodide. In addition, reactive oxygen species (ROS) generation was measured by fluorescence using DCFH-DA staining, and sulfhydryl concentration by spectrophotometry. The in vivo antitumor activity of the polyphenolic fraction (25 mg/kg) was evaluated in a xenograft model in nu/nu mice. In vivo proapoptotic effect was also evaluated by immunohistochemistry using anti-caspase 3 and anti-Bcl-2 antibodies. The results showed that tested products exert colorectal cancer cell cytotoxicity. Besides, the tested products induced a significant increase (p < 0.05) of intracellular ROS generation, and a depletion of sulfhydryl concentration in HCT15 cells. The polyphenolic fraction arrested tumor growth and induced apoptosis in the xenograft mice model. These results demonstrate the cytotoxic activity of T. testudinum metabolites associated, at least, with ROS overproduction and pro-apoptotic effects. Here we demonstrated for the first time the antitumor activity of a T. testudinum polar extract in a xenograft mice model. These results suggest the potential use of T. testudinum marine plant metabolites as adjuvant treatment in cancer therapy.

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Synthetic investigation on chirally pure Mannich derivatives of pseudophenylpropanolamine and their anticancer properties against HepG-2 cells with inhibition of JAK2/STAT3

RSC Advances ◽

10.1039/c6ra22480f ◽

2016 ◽

Vol 6 (99) ◽

pp. 96946-96962 ◽

Cited By ~ 6

Author(s):

C. Balachandran ◽

K. Chennakesava Rao ◽

Y. Arun ◽

N. Emi ◽

N. Yamamoto ◽

...

Keyword(s):

Mice Model ◽

Anticancer Properties ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway ◽

Xenograft Mice Model ◽

Xenograft Mice ◽

Derivatives Of ◽

Synthetic Investigation

In vitro and in vivo anticancer activity of compound 3a was proved as a novel blocker of JAK2/STAT3 signaling pathway and exerts both anti-proliferative and apoptotic activities in HepG-2 cells with xenograft mice model.

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In Vivo Evaluation of Curcumin-loaded Nanoparticles in a A549 Xenograft Mice Model

Asian Pacific Journal of Cancer Prevention ◽

10.7314/apjcp.2013.14.1.409 ◽

2013 ◽

Vol 14 (1) ◽

pp. 409-412 ◽

Cited By ~ 57

Author(s):

Hai-Tao Yin ◽

De-Geng Zhang ◽

Xiao-Li Wu ◽

Xin-En Huang ◽

Gang Chen

Keyword(s):

Mice Model ◽

In Vivo Evaluation ◽

Xenograft Mice Model ◽

Xenograft Mice

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Pectolinarigenin Suppresses the Tumor Growth in Nasopharyngeal Carcinoma

Cellular Physiology and Biochemistry ◽

10.1159/000447879 ◽

2016 ◽

Vol 39 (5) ◽

pp. 1795-1803 ◽

Cited By ~ 11

Author(s):

Chengyu Wang ◽

Yin Cheng ◽

Hongyi Liu ◽

Yaping Xu ◽

Hu Peng ◽

...

Keyword(s):

Flow Cytometry ◽

Tumor Growth ◽

Cell Apoptosis ◽

Severe Toxicity ◽

Dependent Manner ◽

Mice Model ◽

Xenograft Mice Model ◽

Subcutaneous Xenograft ◽

Xenograft Mice

Background/Aims: Nasopharyngeal cancer (NPC) is one of the common human malignant diseases all over the world, and chemotherapy remains the main therapy for NPC. However, the survival and life quality of NPC patients are still very poor. Thus, novel and selective anti-tumor agents are pressingly needed. Our previous study identified pectolinarigenin as a novel effective anti-tumor drug candidate for NPC. In this study, we further investigated its anti-tumor activities and explored the potential molecular mechanism. Methods: NPC C666-1 cells were cultured and treated by pectolinarigenin. Cell proliferation assay, colony formation assay, Transwell assay and wound healing assay were conducted and cell apoptosis was detected by flow cytometry. Mitochondrial transmembrane potential and ROS were also observed. NPC subcutaneous xenograft mice model was established to evaluate the anti-tumor effect of pectolinarigenin in vivo. Results: We observed that treatment of pectolinarigenin inhibited cell viability and cell migration of NPC C666-1 cells in concentration- and time-dependent manner. Pectolinarigenin induced cell apoptosis in C666-1 cells detected by flow cytometry analysis, which was associated with the activation of mitochondrial-related apoptosis and the accumulation of reactive oxygen species (ROS). Pectolinarigenin also activated caspase signaling pathway. The in vivo experiment of subcutaneous xenograft mice model also indicated that the administration of pectolinarigenin could decrease the tumor growth of NPC and no severe toxicity was observed. Conclusions: Based on our findings, we conclude that pectolinarigenin could suppress the tumor growth of NPC, which verifies it as a new therapeutic agent for treating this devastating disease.

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Targeting REV7 effectively reverses 5-FU and oxaliplatin resistance in colorectal cancer

Cancer Cell International ◽

10.1186/s12935-020-01668-z ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Xianjun Sun ◽

Wenhou Hou ◽

Xin Liu ◽

Jie Chai ◽

Hongliang Guo ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Viability ◽

Research Effort ◽

Translesion Synthesis ◽

Xenograft Model ◽

Mice Model ◽

Cell Viability Assay ◽

Viability Assay ◽

Xenograft Mice Model

Abstract Background Despite an enormous research effort, patients diagnosed with advanced colorectal cancer (CRC) still have low prognosis after surgical resection and chemotherapy. The major obstacle for CRC treatment is chemoresistance to front line anti-cancer drugs, such as 5-fluorouracil (5-FU) and oxaliplatin. However, the mechanism of chemoresistance to these drugs remains unclear. Methods Cell viability to 5-FU and oxaliplatin was measured by the CellTiter-Glo® 2.0 Cell Viability Assay. The endogenous REV7 protein in CRC cells was detected by western blotting. The translesion synthesis (TLS) events were measured by plasmid-based TLS efficiency assay. Cell apoptosis was evaluated by caspase3/7 activity assay. The in vivo tumor progression was analyzed by HT29 xenograft mice model. Results In this study, we found that expression of REV7, which is a key component of translesion synthesis (TLS) polymerase ζ (POL ζ), is significantly increased in both 5-FU and oxaliplatin resistant CRC cells. TLS efficiency analysis revealed that upregulated REV7 protein level results in enhanced TLS in response to 5-FU and oxaliplatin. Importantly, inhibition of REV7 by CRISPR/Cas9 knockout exhibited significant synergy with 5-FU and oxaliplatin in cell culture and murine xenograft model. Conclusion These results suggest that combination of REV7 deficiency and 5-FU or oxaliplatin has strong inhibitory effects on CRC cells and identified REV7 as a promising target for chemoresistant CRC treatment.

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