scholarly journals Celastrol Attenuates the Invasion and Migration and Augments the Anticancer Effects of Bortezomib in a Xenograft Mouse Model of Multiple Myeloma

2018 ◽  
Vol 9 ◽  
Author(s):  
Muthu K. Shanmugam ◽  
Kwang S. Ahn ◽  
Jong H. Lee ◽  
Radhamani Kannaiyan ◽  
Nurulhuda Mustafa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Mouse Model ◽  
Xenograft Mouse Model ◽  
Invasion And Migration ◽  
Anticancer Effects ◽  
And Migration

scholarly journals Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-κB regulated gene products in multiple myeloma xenograft mouse model

Oncotarget ◽  
2013 ◽  
Vol 5 (3) ◽  
pp. 634-648 ◽  
Author(s):  
Kodappully Sivaraman Siveen ◽  
Nurulhuda Mustafa ◽  
Feng Li ◽  
Radhamani Kannaiyan ◽  
Kwang Seok Ahn ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Mouse Model ◽  
Gene Products ◽  
Xenograft Mouse Model ◽  
Anticancer Effects

Cucurbitacins: A Systematic Review of the Phytochemistry and Anticancer Activity

2015 ◽  
Vol 43 (07) ◽  
pp. 1331-1350 ◽  
Author(s):  
Yuee Cai ◽  
Xiefan Fang ◽  
Chengwei He ◽  
Peng Li ◽  
Fei Xiao ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Mapk Signaling ◽  
Research Progress ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Cycle Arrest ◽  
Anticancer Effects ◽  
And Migration

Cucurbitacins are highly oxidized tetracyclic triterpenoids that are widely present in traditional Chinese medicines (Cucurbitaceae family), possess strong anticancer activity, and are divided into 12 classes from A to T with over 200 derivatives. The eight most active cucurbitacin components against cancer are cucurbitacin B, D, E, I, IIa, L glucoside, Q, and R. Their mechanisms of action include antiproliferation, inhibition of migration and invasion, proapoptosis, and cell cycle arrest promotion. Cucurbitacins are also found to be the inhibitors of JAK-STAT3, Wnt, PI3K/Akt, and MAPK signaling pathways, which play important roles in the apoptosis and survival of cancer cells. Recently, new studies have discovered synergistic anticancer effects by using cucurbitacins together with clinically approved chemotherapeutic drugs, such as docetaxel and methotrexate. This paper provides a summary of recent research progress on the anticancer property of cucurbitacins and the various intracellular signaling pathways involved in the regulation of cancer cell proliferation, death, invasion, and migration. Therefore, cucurbitacins are a class of promising anticancer drugs to be used alone or be intergraded in current chemotherapies and radiotherapies to treat many types of cancers.

scholarly journals Echinacoside Suppresses the Progression of Breast Cancer by Downregulating the Expression of miR-4306 and miR-4508

2021 ◽  
Vol 20 ◽  
pp. 153473542110626
Author(s):  
Peng Bian ◽  
Chuan Liu ◽  
Wei Hu ◽  
Yu Ding ◽  
Shusheng Qiu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Antitumor Effect ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Anticancer Effects ◽  
And Migration ◽  
Cancer Tissues

The main treatment of breast cancer includes surgical resection, radiotherapy, chemotherapy, endocrine therapy, and molecular targeted therapy, but the outcomes remain unsatisfactory. Previous studies demonstrated that echinacoside, microRNA (miRNA/miR)-4306 and miR-4508 were associated with lymph node metastasis, chemoresistance and self-renewal capability in breast cancer, but in-depth studies on the underlying mechanism of their anticancer effects have not been performed to date. In order to identify the role of miR-4306 and miR-4508, and the mechanism of the antitumor effect of echinacoside in breast cancer, the present study first examined the expression of miR-4306 and miR-4508 in breast cancer tissues to examine their possible role in the development of breast cancer, then evaluated the effect of echinacoside on the expression of miR-4306 and miR-4508 on the viability, apoptosis, cell cycle, migration, and invasion abilities of breast cancer cells to explore the anti-cancer effect of echinacoside and the involvement of miR-4306 and miR-4508. Finally, the breast cancer cells and mice bearing breast cancer xenografts were treated with echinacoside and inhibitors of miR-4508 or miR-4306 to confirm their role on the anticancer effect of echinacoside. The results showed that miR-4306 and miR-4508 were decreased in breast cancer tissues and cells. Echinacoside inhibited cell proliferation, invasion and migration, and promoted the apoptosis of breast cancer cells by downregulating the expression of miR-4306 and miR-4508. In conclusion, this is the first study to show the association between echinacoside and miRNAs in cancer. The present study elucidates an underlying molecular mechanism of the antitumor effect of echinacoside on breast cancer, and thus may contribute to preventive and therapeutic strategies for breast cancer.

Effect of IL-15-Mediating IFN-γ on HTR-8/SVneo Cells and a Preeclampsia Mouse Model Induced by Lipopolysaccharides

2021 ◽  
pp. 1-10
Author(s):  
Xiao-Lu Wang
Keyword(s):  
Mouse Model ◽  
Morphological Changes ◽  
Kidney Injury ◽  
Annexin V ◽  
Urine Protein ◽  
Junctional Zone ◽  
Glycogen Accumulation ◽  
Invasion And Migration ◽  
Ifn Γ ◽  
And Migration

<b><i>Objective:</i></b> Determine the effect of interleukin (IL)-15 on HTR-8/SVneo cells and a preeclampsia (PE) mouse model induced by LPS. <b><i>Methods:</i></b> Transwell and Annexin-V-FITC/PI assays were performed in HTR-8/SVneo cells transfected with IL-15 activation plasmid/siRNA prior to LPS treatment. Additionally, pregnant mice were injected with LPS and IL-15 siRNA followed by measurement of systolic blood pressure (SBP), urine protein, and serum NO. HE staining was used to observe the morphological changes of the placenta and kidney. Glycogen accumulation was detected using Best’s carmine. qRT-PCR, Western blotting, and ELISA were performed to detect mRNA and protein expression. <b><i>Results:</i></b> LPS increased IL-15 and IFN-γ expression in HTR-8/SVneo cells, and IL-15 positively regulated IFN-γ expression in LPS-induced HTR-8/SVneo cells. Moreover, LPS promoted apoptosis and reduced the invasion and migration of HTR-8/SVneo cells, which was, further, promoted by IL-15 overexpression but attenuated by IL-15 inhibition. Furthermore, LPS increased SBP and urine protein but decreased serum NO in mice, and these factors were reversed by IL-15 siRNA. Downregulation of IL-15 also mitigated kidney injury and improved pregnancy outcomes in LPS-induced PE mice. A significantly thicker junctional zone (JZ) and thinner labyrinth layer were found in placentas of PE mice treated with IL-15 siRNA, along with increased glycogen trophoblast cells in the JZ. Moreover, decreased IFN-γ and <i>NKp46</i> were found in placentas of PE mice treated with IL-15 siRNA. <b><i>Conclusion:</i></b> IL-15 inhibition reduced cell apoptosis and increased the invasive and migratory abilities of LPS-induced HTR-8/SVneo cells, thereby alleviating the PE-like phenotype and improving pregnancy outcome.

scholarly journals NEK2 Promotes Bortezomib Resistance through Enhancing Autophagy By Upregulation of Beclin1 in Multiple Myeloma Cells

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4332-4332
Author(s):  
Jiliang Xia ◽  
Yanjuan He ◽  
Bin Meng ◽  
Jingyu Zhang ◽  
Xuan Wu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Drug Resistance ◽  
Mouse Model ◽  
Protein Level ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Transcriptional Level ◽  
Newly Diagnosed ◽  
Multidrug Resistance Proteins ◽  
Xenograft Mouse Model

Background: Multiple Myeloma(MM) is a neoplastic plasma-cell disorder that is characterized by clonal proliferation of malignant of plasma cells in the bone microenvironment, and monoclonal protein in the blood or urine. Drug resistance is one of the main causes of cancer relapse, thus exploring the molecular mechanisms of drug resistance is important for improving therapeutic effect in MM. Our previous publications have demonstrated NEK2 mediated drug resistance via up-regulation of multidrug resistance proteins. In this study, we found autophagy was involved in NEK2 induced Bortezomib resistance in MM cells. Materials and Methods: Primary CD138 positive cells derived from healthy donors(n=6), newly diagnosed MM patients(n=9) and relapsed MM patients(n=7) were isolated by using beads conjugated with human CD138 antibody. Immunofluorescence was performed to detect the expression of NEK2 and LC3B(LC3B-Ⅰand LC3B-Ⅱ) in primary CD138 positive cells. DALGreen was used to detect autolysosome in MM cells. TAP-MS and CO-IP were used to analyze NEK2 interacting proteins. Cell proliferation were examined with soft agar colony formation and cell count. Cell apoptosis was tested through detecting cleaved Caspase3 and cleaved PARP by western blot. Xenograft mouse model of MM were prepared by subcutaneous injection of MM cells(KMS11 NEK2 OE+Scramble, KMS11 NEK2 OE+Beclin1 sh) into immunodeficient B-NDG mouse(1×106 cell/mice). Results: Firstly, immunofluorescence results showed NEK2 expression and LC3B-Ⅱ labeled autophagosome were significantly increased in CD138 positive cells derived from relapsed MM patients as compared with newly diagnosed MM patients and HD. Moreover, over-expression of NEK2 enhanced antophagy, while knockdown of NEK2 suppressed autophagy in MM cells. To explore the underling mechanisms of NEK2 induces autophagy in MM cells, TAP-MS was performed. As a result, Beclin1, an important regulatory protein of autophagy, was identified as NEK2 interacting protein, which was further confirmed by CO-IP in MM cell lines KMS11 and RPMI 8226. Additionally, we found that NEK2 regulated the expression of Beclin1 at protein level, but not at transcriptional level. Subsequent mechanism study indicated NEK2 increased the stability of Beclin1 protein through USP7 mediated deubiquitination, thereby promoting the formation of the Beclin1-Vps15-Vps34 complex, and finally, enhancing autophagy in MM cells. Furthermore, knockdown of Beclin1 significantly suppressed NEK2 induced autophagy in MM cells. Alternatively, down-regulation of Beclin1 overcame NEK2 mediated Bortezomib resistance in xenograft mouse model of MM , suggesting that targeting Beclin1 is a promising approach to therapy MM patients with high NEK2 expression. Conclusion: Our findings revealed NEK2 induced autophagy through up-regulation of Beclin1 at protein level, and confirmed autophagy was involved in NEK2 mediated Bortezomib resistance in MM. Taken together, this study provided novel insight into treating relapsed MM patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Characterizing the Tumor Suppressor Role of CEACAM1 in Multiple Myeloma

2018 ◽  
Vol 45 (4) ◽  
pp. 1631-1640 ◽  
Author(s):  
Jinge Xu ◽  
Bin Liu ◽  
Shoubao Ma ◽  
Jubin Zhang ◽  
Yuhan Ji ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Flow Cytometry ◽  
Tumor Suppressor ◽  
Carcinoembryonic Antigen ◽  
Cell Lines ◽  
Western Blotting ◽  
Cell Invasion ◽  
Caspase 3 ◽  
Invasion And Migration ◽  
And Migration

Background/Aims: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), also known as CD66a, is a member of the immunoglobulin (Ig) superfamily that belongs to the carcinoembryonic antigen (CEA) family which plays a dual role in cancer. Previous studies showed high expression of CEACAM1 in multiple myeloma (MM). The aim of this study was to investigate the biological consequences of CEACAM1 overexpression in MM. Methods: pEGFP-N1-CEACAM1 and pcDNA3.1-CEACAM1 expression plasmids were transfected into U-266 and RPMI8266 cell lines . Effect of CEACAM1 overexpression on the proliferation of two cell lines were tested by the CCK8 assay. Cell cycle and Apoptotic changes after CEACAM1 transfection were examined with AnnexinV–FITC/PI by flow cytometry. Hochest staining assay was used to confirm the apoptotic changes. Caspase-3 activity was examined by Western blotting. The cell invasion and migration activity change after CEACAM1 transfection were performed by well chamber assays and a wound healing, respectively. MMP-2 and MMP-9 proteins expression were detected by Western blotting. Flow cytometry immunophenotyping was be evaluated on myeloma cells from bone marrow taken from 50 patients with symptomatic MM newly diagnosed. The correlations between CEACAM1 expression levels and the clinical features across all groups were investigated. Results: CEACAM1 overexpression significantly suppressed MM cell proliferation, induced cell apoptosis, and inhibited cell invasion and migration possibly through activation of caspase-3 and downregulation of MMP-2 and MMP-9. CEACAM1 expression in patients with DS stage I was more frequent (61.5%) than those with DS stage II (21.1%) or III (22.2%). Furthermore, patients with β2-microglobulin levels equal to or less than 3.5 mg/L had higher CEACAM1 expression than those with β2-microglobulin levels greater than 3.5 mg/L. Conclusion: Our findings suggest that CEACAM1 may act as a tumor suppressor in MM.

Depletion of Host CD122+ Cells Facilitates Widespread Skeletal Multiple Myeloma Engraftment in NOD/SCID Recipients

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2734-2734
Author(s):  
Lisa M Freeman ◽  
Eugene Petcu ◽  
Robert Smith ◽  
Ali Salajegheh ◽  
Peter Diamond ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Mouse Model ◽  
Cell Lines ◽  
Hind Limb ◽  
Clinical Manifestations ◽  
Disease Symptoms ◽  
Xenograft Mouse Model ◽  
Post Transplant ◽  
Human Multiple Myeloma ◽  
Hind Limb Paralysis

Abstract To facilitate human multiple myeloma (MM) engraftment into NOD/SCID recipients, mice were depleted of CD122+ cells (NK and myeloid cells) by antibody-mediated ablation prior to transplantation with the MM cell lines (RPMI8226, RPMI8226-TGL or U226). The MM engraftment, skeletal MM distribution, osteolysis, lambda chain paraprotein and associating disease symptoms in CD122+ cell-depleted and CD122+ cellreplete mice were compared. The CD122+ cell-depleted mice engrafted at a significantly higher frequency with human CD38+, CD56+, PCA-1+ and CD138+ cells. In the CD122+ cell-depleted mice, bioluminescence MM signal involved the whole mouse compared to limited imaging signal in the CD122+ cell-replete mice. The majority 88%–100% of CD122+ cell-depleted mice developed MM engraftment throughout the appendicular and axial skeletons with osteolysis and rare subcutaneous plasmacytomas (11% of mice). Serum paraprotein appeared earlier at 4–5 weeks post-transplant in CD122+ cell-depleted mice and continued to increase during the 12–13 weeks of analysis. The majority, 92% of CD122+ cell-depleted mice developed hind-limb paralysis and had a significantly shortened 45 day survival. Thus, depletion of CD122+ cells reduced resistance to the human MM and produced a new MM xenograft-NOD/SCID model that recapitulates the clinical manifestations of MM and eliminates the major limitations associated with the published MM xenograft-mouse model.

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