TRB3 is elevated in psoriasis vulgaris lesions and mediates HaCaT cells proliferation in vitro

Psoriasis is a chronic skin disease characterized by abnormal keratinocyte proliferation and differentiation, inflammation, and angiogenesis. Overexpression of tribbles homolog3 (TRB3), which belongs to the tribbles family of pseudokinases, has been found in several human tumors and metabolic diseases, but its role in psoriasis has not been fully clarified. The aim of this study is to investigate the expression of TRB3 in psoriasis and explore its roles in the proliferation of keratinocytes. Twenty-four patients with psoriasis vulgaris were recruited for the study. Diagnosis of psoriasis was based on clinical and histologic examinations. Immunohistochemistry and real-time reverse transcription PCR (RT-PCR) were performed to determine protein and messenger RNA (mRNA) expression of TRB3 in psoriasis lesions. 5-Bromo-2-deoxyUridine (BrdU) incorporation assay were performed for cell proliferation. Cell cycle distribution was assessed by flow cytometry analysis. The levels of TRB3 is elevated in psoriatic lesions compared with psoriatic non-lesions. The HaCat cells expressed the TRB3 gene. We found TRB3 silencing to significantly inhibit HaCat cell proliferation. Furthermore, the specific knockdown of TRB3 slowed down the cell cycle at the gap 0/first gap phase. In conclusion, our data suggest that TRB3 is overexpressed in lesions of patients with psoriasis and may be involved in the abnormal proliferation of keratinocytes. Therefore, TRB3 may be a potential therapeutic target for psoriasis.

Download Full-text

191 RISK ASSESSMENT OF BISPHENOL A, AN ENDOCRINE DISRUPTOR, VIA PROLIFERATIVE EFFECT ON THE GROWTH OF ESTROGEN-DEPENDENT OVARIAN CANCER IN CELLULAR AND ANIMAL MODELS

Reproduction Fertility and Development ◽

10.1071/rdv25n1ab191 ◽

2013 ◽

Vol 25 (1) ◽

pp. 244

Author(s):

K.-A. Hwang ◽

K.-C. Choi

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cell Proliferation ◽

Bisphenol A ◽

Cancer Cells ◽

The Body ◽

Brdu Incorporation ◽

Ovarian Cancer Cells ◽

Tumour Proliferation

One of estrogens in the body, 17β-oestradiol (E2), is a pleiotropic hormone that regulates the growth and differentiation of many tissues and also acts as a mitogen that promotes the development and proliferation of hormone-responsive cancers such as breast and ovarian carcinomas. Xenoestrogens are chemical compounds that imitate oestrogen in living organisms and are classified as a type of endocrine-disrupting chemical (EDC). Bisphenol A (BPA) is a widely used industrial compound, and also known as an EDC and especially a xenoestrogen. In this study, we examined the effect of E2 or BPA on the cell growth of BG-1 ovarian cancer cells in vivo and in vitro. In the cell proliferation assay in vitro, E2 or BPA increased the growth of the BG-1 ovarian cancer cells expressing oestrogen receptors (ER). Their proliferation activity was reversed by the treatment of ICI 182 780, a well-known antagonist of ER, which demonstrates that the cell proliferation by E2 or BPA is mediated by ER and BPA certainly acts as a xenoestrogen in the BG-1 ovarian cancer cells. Clearly, E2 and BPA increased the expression of cyclin D1, a factor responsible for the G1/S cell cycle transition. These reagents also decreased the expression of p21, a potent cyclin-dependent kinase (CDK) inhibitor that arrests the cell cycle in the G1 phase. As a result, they promoted the proliferation of BG-1 cells via upregulation of the cell cycle progression. In mice xenograft models transplanted with BG-1 ovarian cancer cells, E2 or BPA administration significantly induced the tumour proliferation compared with vehicle (corn oil) treatment for 10 weeks, which was identified by the measurement of tumour volume and histological analysis on tumour tissues such as hematoxylin and eosin (H&E) staining and BrdU incorporation assay. Taken together, as an EDC having a xenoestrogenic activity, BPA was demonstrated to have a risk of tumour proliferation in oestrogen-dependent cancers such as ovarian cancer. This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Education, Science and Technology (MEST) of government of Korea (no. 2011-0015385).

Download Full-text

Insulin Stimulates Goose Liver Cell Growth by Activating PI3K-AKT-mTOR Signal Pathway

Cellular Physiology and Biochemistry ◽

10.1159/000438650 ◽

2016 ◽

Vol 38 (2) ◽

pp. 558-570 ◽

Cited By ~ 10

Author(s):

Chunchun Han ◽

Shouhai Wei ◽

Qi Song ◽

Fang He ◽

Xiangping Xiong ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Dna Synthesis ◽

Protein Content ◽

Mrna Level ◽

Signal Pathway ◽

Mtor Pathway ◽

Brdu Incorporation ◽

Primary Hepatocytes

Background/Aims: Recent studies have suggested a crucial role for PI3K-Akt-mTOR pathway in regulating cell proliferation, so we hypothesize that insulin acts goose hepatocellular growth by PI3K-Akt-mTOR signal pathway. Because the physiological status of liver cells in vitro is different from that in vivo, a simplified cell model in vitro was established. Methods: Goose primary hepatocytes were isolated and incubated in either no addition as a control or insulin or PI3K-Akt-mTOR pathway inhibitors or co-treatment with glucose and PI3K-Akt-mTOR pathway inhibitors; Then, cell DNA synthesis and cell cycle analysis were detected by BrdU-incorporation Assay and Flow cytometric analysis; the mRNA expression and protein expression of factors involved in the cell cycle were determined by Real-Time RT-PCR, ELISA, and western blot. Results: Here we first showed that insulin evidently increased the cell DNA synthesis, the mRNA level and protein content of factors involved in the cell proliferation of goose primary hepatocytes. Meanwhile, insulin evidently increased the mRNA level and protein content of factors involved in PI3K-Akt-mTOR pathway. However, the up-regulation of insulin on cell proliferation was decreased significantly by the inhibitors of PBK-Akt-mTOR pathway, LY294002, rapamycin or NVP-BEZ235. Conclusion: These findings suggest that PI3K-Akt-mTOR pathway plays an essential role in insulin-regulated cell proliferation of goose hepatocyte.

Download Full-text

A Randomized, Double-Blind, Controlled Clinical Study on the Curative Effect of Huaier on Mild-to-Moderate Psoriasis and an Experimental Study on the Proliferation of Hacat Cells

BioMed Research International ◽

10.1155/2018/2372895 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Dongqiang Su ◽

Xuening Zhang ◽

Likun Zhang ◽

Jin Zhou ◽

Feng Zhang

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Life Quality ◽

The Body ◽

Control Group ◽

Hacat Cells ◽

Antitumor Effects ◽

Double Blind ◽

Keratinocyte Proliferation ◽

Number Of Patients

The antitumor effects of Huaier have been recently revealed. However, no research has been conducted on the effects of Huaier on keratinocyte proliferation and for the treatment of psoriasis. Hacat cells were treated with different concentrations of Huaier for different periods of times. The effects on cell proliferation and vitality and on the cell cycle were detected. Patients with mild-to-moderate psoriasis were randomized and divided into two groups in a double-blind manner. The experimental group was given sugar-free Yinxie granules and Huaiqihuang (HQH) granules, and the control group was given sugar-free Yinxie granules and placebo. After 4 weeks, various therapeutic indexes were compared. Huaier significantly inhibited Hacat cell proliferation, suppressed vitality, and blocked the cell cycle in the G1 phase compared with the control group (P < 0.01, respectively). After treatment for 4 weeks, the number of patients between the two groups that experienced a 50% reduction in the Psoriasis Area and Severity Index (PASI 50), PASI 75 and PASI 90, was significantly different (P <0.01). The body surface area (BSA) affected by psoriasis and static physician’s global assessment (sPGA) was significantly reduced (P < 0.01); additionally, a significant improvement in the Dermatology Life Quality Index (DLQI) (P < 0.01) was observed. Huaier has shown promising effects in both clinical and experimental setting in this preliminary study and it might provide some benefit in the treatment of psoriasis vulgaris in the future.

Download Full-text

The ETS Transcription Factor ETV7 Exhausts Hematopoietic Stem Cells By Enhancing The Cell Cycle Entry and Cell Proliferation

Blood ◽

10.1182/blood.v122.21.733.733 ◽

2013 ◽

Vol 122 (21) ◽

pp. 733-733 ◽

Cited By ~ 1

Author(s):

Masashi Numata ◽

Ramon Klein Geltink ◽

Gerard Grosveld

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Tumor Suppressor ◽

Brdu Incorporation ◽

Post Transplantation ◽

Hematopoietic Stem ◽

Cell Cycle Entry ◽

Fcm Analysis

Abstract Although ETS-transcription factors play a role in normal and malignant hematopoiesis, their function in hematopoietic stem cells (HSCs) and leukemia initiating cells (LICs) is largely unknown. We originally identified the novel ETS transcription factor ETV7, which is highly homologous to ETV6/TEL, a frequent target of chromosomal translocation in human leukemia. Previously we have shown that ETV7 is a hematopoietic oncoprotein that requires cooperating mutations to induce leukemic transformation. Microarray analysis revealed that ETV7 expression is upregulated in 70% of pediatric ALL and AML samples. This indicates a possible oncogenic function of ETV7 in a variety of leukemias, although the molecular mechanism of ETV7-mediated leukemogenesis remains to be elucidated. ETV7 is widely but not abundantly expressed in various human tissues. Recently we found that overexpression of ETV7 in human cord blood-derived CD34+ cells depletes the number of CD34+CD38- HSCs. In addition, ETV7-transduced cells slightly accerelated cell proliferation. These results suggest that overexpression of ETV7 activates cell proliferation in primary human CD34+cells and depletes the number of HSCs. Here, by using a mouse model, we show that ectopic expression of ETV7 in quiescent HSCs accelerates their cell cycle entry and proliferation, leading to the exhaust of HSCs in mice. The ETV7 gene locus is deleted in part of the rodents including the mouse despite its high level of conservation among vertebrates. To circumvent this limitation, we have generated an ETV7 BAC transgenic mouse that carries a single copy of a human BAC DNA containing the ETV7 gene locus. In flow cytometry (FCM) analysis of wild type (WT) and ETV7 bone marrow (BM)-derived Lin-Sca1+cKit+(LSK) cells, the size and frequency of LT(long term)-HSCs (CD48-CD150+LSK) in ETV7 LSK was 2-fold lower than that in WT LSK, while the frequency of LSK and hematopoietic common progenitor cells in WT and ETV7 BM are similar. As compared with WT-LSK, ETV7-LSK showed a significantly decreased number of myeloid progenitor colonies in both the initial plating (MC1) and replating of MC1 colonies (MC2) in methylcellulose colony formation assay in vitro. To assess the ETV7 HSC function contributing to blood cell generation in vivo, we performed competitive repopulation assays. In agreement with the in vitro results, the repopulation ability of HSC is significantly compromised in ETV7 mice as measured 7 weeks post transplantation. This defect was even more pronounced 16 weeks post transplantation. Since enhanced cell cycle entry is known to cause loss of hematopoietic stem/progenitor cells (HSPCs) through the activation of a tumor suppressor response, we quantified p19ARF, p16INK4a, and p21CDKN1A gene expression in LSK cells by qRT-PCR. At day 6 and day 9 of in vitro culture, ETV7 LSK cells activated the p19ARF, p16INK4a, and p21CDKN1A genes about 2-fold greater than WT LSK cells. To measure the de novo DNA replication of HSPCs in vivo, BrdU-pulse labeled BM cells were harvested and BrdU incorporation was quantified by FCM analysis. ETV7 LSK cells showed elevated BrdU incorporation compared with that of WT. In addition, Hoechst33342/Pyronin Y staining revealed that ETV7 LSK enhanced transition from G0 to the G1 phase of the cell cycle, suggesting that ETV7 forced cell cycle entry of quiescent HSCs. Finally to clarify the involvement of the CDKN2A tumor suppressor in ETV7-associated HSC exhaustion, we examined the frequency of HSPCs in CDKN2A-/- and ETV7+/-CDKN2A-/- LSK cells in vivo by FCM analysis. Loss of CDKN2A but not ARF restored the depletion of ETV7 LT-HSCs. Moreover, loss of CDKN2A rescued the defect of repopulation ability in vivo and self-renewal activity in vitro of ETV7 HSPCs. These results indicate that exhaustion of HSC in ETV7 BM occurred through ETV7-induced activation of cell proliferation and the CDKN2A tumor suppressor pathway in mice. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Inhibition of Proliferation and Induction of Apoptosis by Thymoquinone via Modulation of TGF Family, p53, p21 and Bcl-2α in Leukemic Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520617666170912133054 ◽

2018 ◽

Vol 18 (2) ◽

pp. 210-215 ◽

Cited By ~ 3

Author(s):

Mona Diab-Assaf ◽

Josiane Semaan ◽

Marwan El-Sabban ◽

Soad K. Al Jaouni ◽

Rania Azar ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

T Cell ◽

Flow Cytometric Analysis ◽

Leukemic Cells ◽

Cell Cycle Distribution ◽

Dependent Manner ◽

Apoptosis Induction ◽

Inhibition Of Proliferation ◽

Human T Cell

Introduction: Adult T-cell leukemia (ATL) is an aggressive form of malignancy caused by human T- cell lymphotropic virus 1 (HTLV-1). Currently, there is no effective treatment for ATL. Thymoquinone has been reported to have anti-cancer properties. Objective: The aim of this study is to investigatthe effects of TQ on proliferation, apoptosis induction and the underlying mechanism of action in both HTLV-1 positive (C91-PL and HuT-102) and HTLV-1 negative (CEM and Jurkat) malignant T-lymphocytes. Materials and Methods: Cells were incubated with different thymoquinone concentrations for 24h. Cell cytotoxicity was assayed using the CytoTox 96® Non-Radioactive Cytotoxicity Assay Kit. Cell proliferation was determined using CellTiter 96® Non-Radioactive Cell Proliferation. Cell cycle analysis was performed by staining with propidium iodide. Apoptosis was assessed using cell death ELISA kit. The effect of TQ on p53, p21, Bcl-2 protein expression was determined using Western blot analysis while TGF mRNA expression was determined by RT-PCR. Results: At non-cytotoxic concentrations of TQ, it resulted in the inhibition of proliferation in a dose dependent manner. Flow cytometric analysis revealed a shift in the cell cycle distribution to the PreG1 phase which is a marker of apoptosis. Also TQ increase DNA fragmentation. TQ mediated its anti-proliferative effect and apoptosis induction by an up-regulation of TGFβ1, p53 and p21 and a down-regulation of TGF-α and Bcl-2α. Conclusion: Thymoquinone presents antiproliferative and proapoptotic effects in ATL cells. For this reason, further research is required to investigate its possible application in the treatment of ATL.

Download Full-text

BRD4 PROTAC degrader ARV-825 inhibits T-cell acute lymphoblastic leukemia by targeting 'Undruggable' Myc-pathway genes

Cancer Cell International ◽

10.1186/s12935-021-01908-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Shuiyan Wu ◽

You Jiang ◽

Yi Hong ◽

Xinran Chu ◽

Zimu Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Acute Lymphoblastic Leukemia ◽

Caspase 3 ◽

Lymphoblastic Leukemia ◽

Rna Seq ◽

Cell Acute Lymphoblastic Leukemia ◽

Bet Protein

Abstract Background T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a high risk of induction failure and poor outcomes, with relapse due to drug resistance. Recent studies show that bromodomains and extra-terminal (BET) protein inhibitors are promising anti-cancer agents. ARV-825, comprising a BET inhibitor conjugated with cereblon ligand, was recently developed to attenuate the growth of multiple tumors in vitro and in vivo. However, the functional and molecular mechanisms of ARV-825 in T-ALL remain unclear. This study aimed to investigate the therapeutic efficacy and potential mechanism of ARV-825 in T-ALL. Methods Expression of the BRD4 were determined in pediatric T-ALL samples and differential gene expression after ARV-825 treatment was explored by RNA-seq and quantitative reverse transcription-polymerase chain reaction. T-ALL cell viability was measured by CCK8 assay after ARV-825 administration. Cell cycle was analyzed by propidium iodide (PI) staining and apoptosis was assessed by Annexin V/PI staining. BRD4, BRD3 and BRD2 proteins were detected by western blot in cells treated with ARV-825. The effect of ARV-825 on T-ALL cells was analyzed in vivo. The functional and molecular pathways involved in ARV-825 treatment of T-ALL were verified by western blot and chromatin immunoprecipitation (ChIP). Results BRD4 expression was higher in pediatric T-ALL samples compared with T-cells from healthy donors. High BRD4 expression indicated a poor outcome. ARV-825 suppressed cell proliferation in vitro by arresting the cell cycle and inducing apoptosis, with elevated poly-ADP ribose polymerase and cleaved caspase 3. BRD4, BRD3, and BRD2 were degraded in line with reduced cereblon expression in T-ALL cells. ARV-825 had a lower IC50 in T-ALL cells compared with JQ1, dBET1 and OTX015. ARV-825 perturbed the H3K27Ac-Myc pathway and reduced c-Myc protein levels in T-ALL cells according to RNA-seq and ChIP. In the T-ALL xenograft model, ARV-825 significantly reduced tumor growth and led to the dysregulation of Ki67 and cleaved caspase 3. Moreover, ARV-825 inhibited cell proliferation by depleting BET and c-Myc proteins in vitro and in vivo. Conclusions BRD4 indicates a poor prognosis in T-ALL. The BRD4 degrader ARV-825 can effectively suppress the proliferation and promote apoptosis of T-ALL cells via BET protein depletion and c-Myc inhibition, thus providing a new strategy for the treatment of T-ALL.

Download Full-text

Modulation effects of hexamethylene bisacetamide on growth and differentiation of cultured human malignant glioma cells

Journal of Neurosurgery ◽

10.3171/jns.1996.84.5.0831 ◽

1996 ◽

Vol 84 (5) ◽

pp. 831-838 ◽

Cited By ~ 13

Author(s):

Xiao-Nan Li ◽

Zi-Wei Du ◽

Qiang Huang

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Malignant Glioma ◽

Culture Media ◽

Morphological Changes ◽

Control Group ◽

Cell Cycle Distribution ◽

Content Type ◽

Hexamethylene Bisacetamide ◽

Human Malignant Glioma

✓ The modulation effects of hexamethylene bisacetamide (HMBA), a differentiation-inducing agent, on growth and differentiation of cells from human malignant glioma cell line SHG-44 were studied. At cytostatic doses (2.5 mM, 5 mM, 7.5 mM, and 10 mM for 15 days), HMBA exerted a marked inhibitory effect on cell proliferation. Exposure to HMBA (5 mM and 10 mM for 12 days) also resulted in an accumulation of cells in G0/G1 phase and a decrease of cells in S phase as analyzed by flow cytometry. The reversible effects of 7.5 mM HMBA and 10 mM HMBA on cell proliferation and 10 mM HMBA on disruption of cell cycle distribution were observed when HMBA was removed from culture media on Day 6 and replaced with HMBA-free media. Colony-forming efficiency (CFE) in soft agar was remarkably decreased by HMBA (2.5 mM, 5 mM, 7.5 mM, and 10 mM for 14 days), and in 7.5 mM HMBA— and 10 mM HMBA—treated cells, the CFEs were reduced to 25% and 12.5%, respectively, of that in untreated cells. Cells treated with HMBA (5 mM and 10 mM for 15 days) remained tumorigenic in athymic nude mice, but the growth rates of the xenografts were much slower than those in the control group. The effects of HMBA on cell proliferation, cell cycle distribution, CFE, and growth of xenografts were dose dependent. A more mature phenotype was confirmed by the morphological changes from spindle shape to large polygonal stellate shape and remarkably elevated expression of glial fibrillary acidic protein in cells exposed to HMBA (5 mM, 10 mM for 15 days). Our results showed that a more differentiated phenotype with marked growth arrest was induced in SHG-44 cells by HMBA.

Download Full-text

LMNB2 promotes the progression of colorectal cancer by silencing p21 expression

Cell Death and Disease ◽

10.1038/s41419-021-03602-1 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Chen-Hua Dong ◽

Tao Jiang ◽

Hang Yin ◽

Hu Song ◽

Yi Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Cell Proliferation ◽

Cell Cycle Progression ◽

Molecular Mechanisms ◽

Gene Set Enrichment Analysis ◽

Molecular Therapy ◽

Cycle Progression ◽

Cancer Tissues

AbstractColorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.

Download Full-text

The Olive Leaves Extract Has Anti-Tumor Effects against Neuroblastoma through Inhibition of Cell Proliferation and Induction of Apoptosis

Nutrients ◽

10.3390/nu13072178 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2178

Author(s):

Fabio Morandi ◽

Veronica Bensa ◽

Enzo Calarco ◽

Fabio Pastorino ◽

Patrizia Perri ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Viability ◽

Cell Cycle Progression ◽

Treatment Strategies ◽

Annexin V ◽

Dependent Manner ◽

Induction Of Apoptosis ◽

Dose Dependent

Neuroblastoma (NB) is the most common extra-cranial solid tumor of pediatric age. The prognosis for high-risk NB patients remains poor, and new treatment strategies are desirable. The olive leaf extract (OLE) is constituted by phenolic compounds, whose health beneficial effects were reported. Here, the anti-tumor effects of OLE were investigated in vitro on a panel of NB cell lines in terms of (i) reduction of cell viability; (ii) inhibition of cell proliferation through cell cycle arrest; (iii) induction of apoptosis; and (iv) inhibition of cell migration. Furthermore, cytotoxicity experiments, by combining OLE with the chemotherapeutic topotecan, were also performed. OLE reduced the cell viability of NB cells in a time- and dose-dependent manner in 2D and 3D models. NB cells exposed to OLE underwent inhibition of cell proliferation, which was characterized by an arrest of the cell cycle progression in G0/G1 phase and by the accumulation of cells in the sub-G0 phase, which is peculiar of apoptotic death. This was confirmed by a dose-dependent increase of Annexin V+ cells (peculiar of apoptosis) and upregulation of caspases 3 and 7 protein levels. Moreover, OLE inhibited the migration of NB cells. Finally, the anti-tumor efficacy of the chemotherapeutic topotecan, in terms of cell viability reduction, was greatly enhanced by its combination with OLE. In conclusion, OLE has anti-tumor activity against NB by inhibiting cell proliferation and migration and by inducing apoptosis.

Download Full-text

Cell-free fat extract promotes tissue regeneration in a tissue expansion model

Stem Cell Research & Therapy ◽

10.1186/s13287-020-1564-7 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Mingwu Deng ◽

Xiangsheng Wang ◽

Ziyou Yu ◽

Yizuo Cai ◽

Wei Liu ◽

...

Keyword(s):

Cell Proliferation ◽

Growth Factor ◽

Collagen Type ◽

Growth Factor Receptor ◽

Tissue Expansion ◽

Nuclear Antigen ◽

Hacat Cells ◽

Expansion Model

Abstract Background Tissue expansion techniques play an important role in plastic surgery. How to improve the quality of the expanded skin and shorten the expansion period are still worth investigating. Our previous studies found that a cell-free fat extract (CEFFE) possessed pro-angiogenic and pro-proliferative activities. However, the role of CEFFE on tissue expansion has remained unclear. The purpose of this study was to evaluate the effect of CEFFE on tissue expansion. Methods A rat tissue expansion model was used. Animals were treated with CEFFE by subcutaneous injection. After 4 weeks of tissue expansion, the skin necrosis and retraction rates were evaluated, the thicknesses of the epidermis and dermis were determined by histological analyses, blood vessel density was measured by anti-CD31 staining, cell proliferation was assessed by proliferating cell nuclear antigen staining, and the expression of specific proteins was evaluated by western blot analyses. In addition, the effects of CEFFE on the proliferation and cell cycle of cultured HaCaT cells were evaluated in vitro. Results CEFFE treatment significantly decreased the necrosis rate and retraction of the expanded skin. The thickness of the epidermal and dermal layers was higher in CEFFE-treated compared to untreated skin. The density of blood vessels and cell proliferation in the epidermis of the expanded skin was improved by CEFFE treatment. In addition, CEFFE treatment significantly increased the expression of the vascular endothelial growth factor receptor, epidermal growth factor receptor, collagen type 1, and collagen type 3. CEFFE also increased the proliferation of HaCaT cells in culture. Conclusions CEFFE improves the quality of the expanded skin by promoting angiogenesis and cell proliferation. It could be potentially used clinically for augmenting tissue expansion.

Download Full-text