scholarly journals Ocotillol Enhanced the Antitumor Activity of Doxorubicin via p53-Dependent Apoptosis

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Hongbo Wang ◽  
Pengfei Yu ◽  
Jing Bai ◽  
Jianqiao Zhang ◽  
Liang Kong ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Apoptosis ◽  
Therapeutic Strategy ◽  
Target Genes ◽  
Tumor Model ◽  
Xenograft Tumor ◽  
Xenograft Tumor Model ◽  
Hoechst Staining ◽  
Dose Dependent ◽  
Mtt Assays

The use of doxorubicin (Dox) was severely constrained by dose-dependent side effects, which might be attenuated by combining a “sensitizer” to decrease its cumulative dosage. In this study, it was investigated whether ocotillol could enhance the antiproliferation activity of Dox. MTT assays and xenograft tumor model were firstly conducted to evaluate the effect of ocotillol on the antitumor activity of Dox. Flow cytometry and Hoechst staining assays were then performed to assess cell apoptosis. Western blot and real-time PCR were finally used to detect the expression of p53 and its target genes. Our results showed ocotillol to enhance Dox-induced cell death in p53 wild-type cancer cells. Compared with Dox alone, Dox with ocotillol (Dox-O) could induce much more cell apoptosis and activate p53 to a much greater degree, which in turn markedly increased expression of proapoptosis genes. The enhanced cytotoxic activity was partially blocked by pifithrin-α, which might be through attenuating the increased apoptosis. Furthermore, ocotillol significantly increased the antitumor activity of Dox in A549 xenograft tumor in nude mice. These findings indicated that ocotillol could potentiate the cytotoxic effect of Dox through p53-dependent apoptosis and suggested that coadministration of ocotillol with Dox might be a potential therapeutic strategy.

Antitumor Activity of γδ T Cells Reactive against Cytomegalovirus-Infected Cells in a Mouse Xenograft Tumor Model

2009 ◽  
Vol 69 (9) ◽  
pp. 3971-3978 ◽  
Author(s):  
Christel Devaud ◽  
Eric Bilhere ◽  
Séverine Loizon ◽  
Vincent Pitard ◽  
Charlotte Behr ◽  
...  
Keyword(s):  
T Cells ◽  
Antitumor Activity ◽  
Γδ T Cells ◽  
Tumor Model ◽  
Xenograft Tumor ◽  
Mouse Xenograft ◽  
Xenograft Tumor Model ◽  
Infected Cells

scholarly journals Synthesis and In Vitro Antitumor Activity of Novel Bivalent β-Carboline-3-carboxylic Acid Derivatives with DNA as a Potential Target

2018 ◽  
Vol 19 (10) ◽  
pp. 3179 ◽  
Author(s):  
Hongling Gu ◽  
Na Li ◽  
Jiangkun Dai ◽  
Yaxi Xi ◽  
Shijun Wang ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Cell Apoptosis ◽  
Docking Studies ◽  
In Vitro Cytotoxicity ◽  
Dependent Manner ◽  
Cycle Arrest ◽  
Dna Binding Affinity ◽  
Dose Dependent ◽  
Mcf 7

A series of novel bivalent β-carboline derivatives were designed and synthesized, and in vitro cytotoxicity, cell apoptosis, and DNA-binding affinity were evaluated. The cytotoxic results demonstrated that most bivalent β-carboline derivatives exhibited stronger cytotoxicity than the corresponding monomer against the five selected tumor cell lines (A549, SGC-7901, Hela, SMMC-7721, and MCF-7), indicating that the dimerization at the C3 position could enhance the antitumor activity of β-carbolines. Among the derivatives tested, 4B, 6i, 4D, and 6u displayed considerable cytotoxicity against A549 cell line. Furthermore, 4B, 6i, 4D, and 6u induced cell apoptosis in a dose-dependent manner, and caused cell cycle arrest at the S and G2/M phases. Moreover, the levels of cytochrome C in mitochondria, and the expressions of bcl-2 protein, decreased after treatment with β-carbolines, which indicated that 6i and 6u could induce mitochondria-mediated apoptosis. In addition, the results of UV-visible spectral, thermal denaturation, and molecular docking studies revealed that 4B, 6i, 4D, and 6u could bind to DNA mainly by intercalation.

scholarly journals Wnt5b-induced PCP/JNK Activation Promotes PD-L1 Expression and the Malignant Phenotype of Non-small Cell Lung Cancer 

2020 ◽  
Author(s):  
Guangping Wu ◽  
Yuan Luo ◽  
Yusai Xie ◽  
Yang Han ◽  
Di Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Tumor Model ◽  
Small Cell ◽  
Xenograft Tumor ◽  
Small Cell Lung ◽  
Malignant Phenotype ◽  
Membrane Recruitment ◽  
Xenograft Tumor Model

Abstract Background: Wnt5b is noncanonical Wnt ligand, and programmed-death ligand 1 (PD-L1) is a targeted agent for immunotherapy, but the mechanism by which Wnt5b regulates PD-L1 expression in non-small cell lung cancer (NSCLC) is unclear. Methods: Wnt5b and PD-L1 expressions were detected in NSCLC specimens by immunohistochemistry. The interrelationship connecting Wnt5b with PD-L1 was verified using dual-luciferase assay, immunofluorescence, coimmunoprecipitation, western blot，real-time PCR and xenograft tumor model. Results: Wnt5b and PD-L1 expressions were positively correlated in NSCLC specimens. Five-year survival time in the group with their coexpression was significantly lower than that without coexpression. Under the effect of Wnt5b, Frizzled-3 (Fzd3) initiated Dishevellde-3 (Dvl-3) membrane recruitment via DEP domain by Dvl-3 phosphorylation, contributing to activate PCP/JNK signaling through the small GTPase Rac1, and then upregulate PD-L1 expression and promote the malignant phenotype of NSCLC in vivo and in vitro. After PD-L1 antibody treatment, Wnt5b induced tumor growth was inhibited significantly in xenograft tumor model. Conclusion: We demonstrate a new signal transduction pathway: Wnt5b initiates Dvl-3 membrane recruitment via DEP domain by Fzd3 so as to promote Rac1–PCP/JNK–PD-L1 pathway, which provides a potential target for clinical intervention and immunotherapy in lung cancer.

miR-9-5p Promotes β-Catenin-Activated Epithelial-To-Mesenchymal Transition of Triple-Negative Breast Cancer Via Targeting LZTS2

2020 ◽  
Author(s):  
Jie Zhang ◽  
Lina Zhang ◽  
Jianlong Wang ◽  
Jing Zhao ◽  
Xuelian Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Suppressor ◽  
Triple Negative Breast Cancer ◽  
Nuclear Export ◽  
Triple Negative ◽  
Tumor Model ◽  
Migration And Invasion ◽  
Xenograft Tumor ◽  
Xenograft Tumor Model ◽  
Low Expression

Abstract Background: Leucine zipper tumor suppressor 2 (LZTS2), an emerging tumor-suppressor, is attenuated in multiple cancers including prostate, lung and colon cancer. However, its expression and upstream regulatory mechanisms in triple negative breast cancer (TNBC) still remain unknown.Materials and methods: The expression of LZTS2 in TNBC and matched para-carcinoma tissues was detected with immunohistochemistry. The correlations between LZTS2 expression and clinicopathological parameters were analyzed. Kaplan-Meier analysis was performed to determine the prognostic role of LZTS2 for TNBC patients. CCK-8, wound healing and transwell assay were used to detect the effect of LZTS2 overexpression on the proliferation, migration and invasion ability, respectively. The bioinformation algorithms were used to reveal the potential upstream regulatory miRNA. Then, dual-luciferase reporter assay was performed to confirm the regulatory effect of the chosen miRNA on the expression of LZTS2. miR-9-5p inhibitor was used to determine the effect of miR-9-5p on the subcellular localization of β-catenin. Then, western blotting was performed to reveal the effect of miR-9-5p on EMT-related proteins in TNBC cells. Xenograft tumor model was established to reveal the effect of miR-9-5p on TNBC progression in vivo.Results: Low expression of LZTS2 was observed in 62 of 95 cases of TNBC tissue. Low expression of LZTS2 was correlated with poor postoperative DFS and OS of TNBC patients. LZTS2 could inhibit the proliferation, migration and invasion ability of TNBC cells. LZTS2 could be downregulated by miR-9-5p in TNBC, and the nuclear export of β-catenin was suppressed. Consequently, miR-9-5p inhibitor downregulated E-cadherin and upregulated N-cadherin, Twist and Vimentin in TNBC cells. Xenograft tumor model showed that miR-9-5p inhibitor could upregulate the expression of LZTS2 and induce nuclear export of β-catenin in TNBC.Conclusions: miR-9-5p contributes to β-catenin-activated EMT via downregulating LZTS2, and thus promotes TNBC progression.

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