Overexpression of human osteopontin increases cell proliferation and migration in human embryo kidney-293 cells

AbstractMalignant tumors are characterized by dysregulated cell growth and the metastasis of secondary tumors. Numerous studies have documented that osteopontin (OPN) plays a key role in regulating tumor progression and metastasis. Here, we show that the overexpression of OPN in human embryo kidney-293 cells significantly increases both the level of cell proliferation, by provoking the G1/S transition, and the level of cell migration in vitro. These findings suggest that augmented OPN contributes to cell growth and motility. Inhibiting OPN or the pathway it stimulates may therefore represent a novel approach for the treatment of primary tumors and associated metastases.

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Targeting mTOR-CCL20 Signaling May Improve Response to Docetaxel in Head and Neck Squamous Cell Carcinoma

International Journal of Molecular Sciences ◽

10.3390/ijms22063046 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3046

Author(s):

Ming-Huei Chou ◽

Hui-Ching Chuang ◽

Yu-Tsai Lin ◽

Ming-Hsien Tsai ◽

Ying-Hsien Kao ◽

...

Keyword(s):

Cell Proliferation ◽

Squamous Cell Carcinoma ◽

Cell Growth ◽

Xenograft Model ◽

Mtor Inhibitors ◽

Cell Proliferation And Migration ◽

And Migration ◽

Hnscc Cell ◽

Proliferation And Migration

Patients with advanced head and neck squamous cell carcinoma (HNSCC) usually show a dismal prognosis. It is this worthwhile to develop new, effective therapeutic regimens for these patients, such as molecular targeted therapy, which is promising as an alternative or combination treatment for HNSCC. The mammalian target of rapamycin (mTOR) pathway, which plays an important role in the carcinogenesis of HNSCC, is the most frequently activated, and is thus worthy of further investigation. In this study, two human HNSCC cell lines, FaDu and SAS, were evaluated for cell growth with trypan blue staining and tumor growth using an orthotopic xenograft model. The immunohistochemical expression of mTOR in the subcutaneous xenograft model and the inhibitory effects of docetaxel on the growth and state of activation of the PI3K/mTOR pathway were also evaluated and examined by colony formation and Western blot, respectively. Cell proliferation and migration were measured by water-soluble tetrazolium salt (WST-1) and OrisTM cell migration assay, respectively. Furthermore, the effects of rapamycin and BEZ235, a phosphatidylinositol 3-kinases (PI3K) and mTOR inhibitor in combination with docetaxel or CCL20 were evaluated in the FaDu and SAS cells. The results showed that the expression of mTOR was significantly higher in the SAS and FaDu xenograft models than in the control. Docetaxel treatment significantly suppressed HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. Additionally, when administered in a dose-dependent fashion, mTOR inhibitors inhibited the growth and migration of the HNSCC cells. This combination was synergistic with docetaxel, resulting in almost complete cell growth and migration arrest. In conclusion, docetaxel significantly inhibited HNSCC cell proliferation and migration in vitro via the PI3K/mTOR/CCL-20 signaling pathway. The synergistic and additive activity of mTOR inhibitors combined with docetaxel shows potential as a new treatment strategy for HNSCC.

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Knockdown CYP2S1 inhibits lung cancer cells proliferation and migration

Cancer Biomarkers ◽

10.3233/cbm-210189 ◽

2021 ◽

pp. 1-9

Author(s):

Huan Guo ◽

Baozhen Zeng ◽

Liqiong Wang ◽

Chunlei Ge ◽

Xianglin Zuo ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Cell Growth ◽

Cancer Cells ◽

Molecular Mechanisms ◽

Lung Cancer Cells ◽

Invasion And Migration ◽

And Migration

BACKGROUND: The incidence of lung cancer in Yunnan area ranks firstly in the world and underlying molecular mechanisms of lung cancer in Yunnan region are still unclear. We screened a novel potential oncogene CYP2S1 used mRNA microassay and bioinformation database. The function of CYP2S1 in lung cancer has not been reported. OBJECTIVE: To investigate the functions of CYP2S1 in lung cancer. METHODS: Immunohistochemistry and Real-time PCR were used to verify the expression of CYP2S1. Colony formation and Transwell assays were used to determine cell proliferation, invasion and migration. Xenograft assays were used to detected cell growth in vivo. RESULTS: CYP2S1 is significantly up-regulated in lung cancer tissues and cells. Knockdown CYP2S1 in lung cancer cells resulted in decrease cell proliferation, invasion and migration in vitro. Animal experiments showed downregulation of CYP2S1 inhibited lung cancer cell growth in vivo. GSEA analysis suggested that CYP2S1 played functions by regulating E2F targets and G2M checkpoint pathway which involved in cell cycle. Kaplan-Meier analysis indicated that patients with high CYP2S1 had markedly shorter event overall survival (OS) time. CONCLUSIONS: Our data demonstrate that CYP2S1 exerts tumor suppressor function in lung cancer. The high expression of CYP2S1 is an unfavorable prognostic marker for patient survival.

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Epinephrine Stimulates Cell Proliferation and Induces Chemoresistance in Myeloma Cells through the β-Adrenoreceptor in vitro

Acta Haematologica ◽

10.1159/000478517 ◽

2017 ◽

Vol 138 (2) ◽

pp. 103-110 ◽

Cited By ~ 5

Author(s):

Yang Liu ◽

Xiaochen Yu ◽

Junling Zhuang

Keyword(s):

Cell Proliferation ◽

Cell Growth ◽

Cell Line ◽

Receptor Subtype ◽

Dependent Manner ◽

Myeloma Cells ◽

U266 Cell ◽

Β Receptor ◽

U266 Cell Line

Objectives: To explore the effect of the β-adrenoreceptor signaling pathway on myeloma cells. Methods: The myeloma U266 cell line was treated with epinephrine and propranolol. Cell proliferation was analyzed by MTS assay. Apoptosis was detected by flow cytometry. The β-receptor subtype and the key enzyme of epinephrine were identified by reverse transcription polymerase chain reaction (RT-PCR). Results: Epinephrine (5-50 μM) promoted U266 cell growth in a dose-dependent manner and neutralized the inhibition effect of bortezomib (25 and 50 ng/mL) in vitro. Cell proliferation was inhibited by a β-receptor antagonist, propranolol, at a concentration of 50-200 μM. The proportions of early and late apoptotic cells were enhanced after treatment with propranolol. The expression of caspase 3/7, 8, and 9 was elevated in propranolol-treated myeloma cells. Both β1- and β2-adrenoceptor mRNAs were expressed in the U266 cell line. Key enzymes dopamine hydroxylase and tyrosinehydroxylase were identified in myeloma cells. Conclusions: Our results reveal that epinephrine stimulates myeloma cell growth in vitro while the β-blocker propranolol has an antiproliferative effect, indicating that stress hormones may trigger the progression of myeloma.

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KIF23 Promotes Gastric Cancer by Stimulating Cell Proliferation

Disease Markers ◽

10.1155/2019/9751923 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 8

Author(s):

Xiao-Long Li ◽

Ya-Ming Ji ◽

Rui Song ◽

Xiao-Ning Li ◽

Lan-Shuan Guo

Keyword(s):

Gastric Cancer ◽

Cell Proliferation ◽

Malignant Tumors ◽

Vital Role ◽

Gastric Cancer Cells ◽

Vitro Assay ◽

Multiple Tumor ◽

Axon Elongation ◽

Underlying Mechanisms

Gastric cancer (GC) is one of the most aggressive malignant tumors with low early diagnosis and high metastasis. Despite progress in treatment, to combat this disease, a better understanding of the underlying mechanisms and novel therapeutic targets is needed. KIF23, which belongs to the KIF family, plays a vital role in various cell processes, such as cytoplasm separation and axon elongation. Nowadays, KIF23 has been found to be highly expressed in multiple tumor tissues and cells, suggesting a potential link between KIF23 and tumorigenesis. Herein, we reported that KIF23 expression was correlated with poor prognosis of gastric cancer and found an association between KIF23 and pTNM stage. An in vitro assay proved that the proliferation of gastric cancer cells was significantly inhibited, which is caused by KIF23 depletion. Additionally, knockdown of KIF23 resulted in a marked inhibition of cell proliferation of gastric cancer in mice, with significant downregulation of Ki67 and PCNA expression. In conclusion, these data indicate that KIF23 is a potential therapeutic target for gastric cancer treatment.

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Enhancing the biocompatibility of siliconepolycarbonate urethane based implant materials

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2019-0114 ◽

2019 ◽

Vol 5 (1) ◽

pp. 453-455 ◽

Cited By ~ 1

Author(s):

Kiriaki Athanasopulu ◽

Larysa Kutuzova ◽

Joana Thiel ◽

Günter Lorenz ◽

Ralf Kemkemer

Keyword(s):

Molecular Weight ◽

Cell Proliferation ◽

Hyaluronic Acid ◽

Cell Growth ◽

Block Copolymers ◽

Cytotoxic Potential ◽

Implant Surface ◽

Characterization Methods ◽

Hard Segments

AbstractPolyurethane-bases block copolymers (TPCUs) are block-copolymers with systematically varied soft and hard segments. They have been suggested to serve as material for chondral implants in joint regeneration. Such applications may require the adhesion of chondrocytes to the implant surface, facilitating cell growth while keeping their phenotype. Thus, aims of this work were (i) to modify the surface of soft biostable polyurethane-based model implants (TPCU and TSiPCU) with high-molecular weight hyaluronic acid (HA) using an optimized multistep strategy of immobilization, and (ii) to evaluate bioactivity of the modified TPCUs in vitro. Our results show no cytotoxic potential of the TPCUs. HAbioactive molecules (Mw =700kDa) were immobilized onto the polyurethane surface via polyethylenimine (PEI) spacers, and modifications were confirmed by several characterization methods. Tests with porcine chondrocytes indicated the potential of the TPCU-HA for inducing enhanced cell proliferation.

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Effect and mechanism of YB-1 knockdown on glioma cell growth, migration, and apoptosis

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmz161 ◽

2020 ◽

Vol 52 (2) ◽

pp. 168-179 ◽

Cited By ~ 1

Author(s):

Huilin Gong ◽

Shan Gao ◽

Chenghuan Yu ◽

Meihe Li ◽

Ping Liu ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Growth ◽

Glioma Cell ◽

Cell Transformation ◽

Malignant Cell ◽

Protein Levels ◽

Glioma Progression

Abstract Y-box binding protein 1 (YB-1) is manifested as its involvement in cell proliferation and differentiation and malignant cell transformation. Overexpression of YB-1 is associated with glioma progression and patient survival. The aim of this study is to investigate the influence of YB-1 knockdown on glioma cell progression and reveal the mechanisms of YB-1 knockdown on glioma cell growth, migration, and apoptosis. It was found that the knockdown of YB-1 decreased the mRNA and protein levels of YB-1 in U251 glioma cells. The knockdown of YB-1 significantly inhibited cell proliferation, colony formation, and migration in vitro and tumor growth in vivo. Proteome and phosphoproteome data revealed that YB-1 is involved in glioma progression through regulating the expression and phosphorylation of major proteins involved in cell cycle, adhesion, and apoptosis. The main regulated proteins included CCNB1, CCNDBP1, CDK2, CDK3, ADGRG1, CDH-2, MMP14, AIFM1, HO-1, and BAX. Furthermore, it was also found that YB-1 knockdown is associated with the hypo-phosphorylation of ErbB, mTOR, HIF-1, cGMP-PKG, and insulin signaling pathways, and proteoglycans in cancer. Our findings indicated that YB-1 plays a key role in glioma progression in multiple ways, including regulating the expression and phosphorylation of major proteins associated with cell cycle, adhesion, and apoptosis.

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Distinct and sequential upregulation of genes regulating cell growth and cell cycle progression during hepatic ischemia-reperfusion injury

AJP Cell Physiology ◽

10.1152/ajpcell.00629.2004 ◽

2005 ◽

Vol 289 (4) ◽

pp. C826-C835 ◽

Cited By ~ 41

Author(s):

Sharon Barone ◽

Tomohisa Okaya ◽

Steve Rudich ◽

Snezana Petrovic ◽

Kathy Tenrani ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Cell Growth ◽

Reperfusion Injury ◽

Cell Cycle Progression ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Catabolic Pathway ◽

Cycle Progression

Ischemia-reperfusion injury (IRI) in liver and other organs is manifested as an injury phase followed by recovery and resolution. Control of cell growth and proliferation is essential for recovery from the injury. We examined the expression of three related regulators of cell cycle progression in liver IRI: spermidine/spermine N-acetyltransferase (SSAT), p21 (a cyclin-dependent kinase inhibitor), and stathmin. Mice were subjected to hepatic IRI, and liver tissues were harvested at timed intervals. The expression of SSAT, the rate-limiting enzyme in the polyamine catabolic pathway, had increased fivefold 6 h after IRI and correlated with increased putrescine levels in the liver, consistent with increased SSAT enzymatic activity in IRI. The expression of p21, which is transactivated by p53, was undetectable in sham-operated animals but was heavily induced at 12 and 24 h of reperfusion and declined to undetectable baseline levels at 72 h of reperfusion. The interaction of the polyamine pathway with the p53-p21 pathway was shown in vitro, where activation of SSAT with polyamine analog or the addition of putrescine to cultured hepatocytes induced the expression of p53 and p21 and decreased cell viability. The expression of stathmin, which is under negative transcriptional regulation by p21 and controls cell proliferation and progression through mitosis, remained undetectable at 6, 12, and 24 h of reperfusion and was progressively and heavily induced at 48 and 72 h of reperfusion. Double-immunofluorescence labeling with antibodies against stathmin and PCNA, a marker of cell proliferation, demonstrated colocalization of stathmin and PCNA at 48 and 72 h of reperfusion in hepatocytes, indicating the initiation of cell proliferation. The distinct and sequential upregulation of SSAT, p21, and stathmin, along with biochemical activation of the polyamine catabolic pathway in IRI in vivo and the demonstration of p53-p21 upregulation by SSAT and putrescine in vitro, points to the important role of regulators of cell growth and cell cycle progression in the pathophysiology and/or recovery in liver IRI. The data further suggest that SSAT may play a role in the initiation of injury, whereas p21 and stathmin may be involved in the resolution and recovery after liver IRI.

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The Antitumor Effect of Curcumin in Urothelial Cancer Cells Is Enhanced by Light Exposure In Vitro

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/6374940 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 6

Author(s):

Frederik Roos ◽

Katherina Binder ◽

Jochen Rutz ◽

Sebastian Maxeiner ◽

August Bernd ◽

...

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Bladder Cancer ◽

Cell Growth ◽

Visible Light ◽

Cancer Cells ◽

Cell Lines ◽

Light Exposure ◽

Bladder Cancer Cells

The natural compound curcumin exerts antitumor properties in vitro, but its clinical application is limited due to low bioavailability. Light exposure in skin and skin cancer cells has been shown to improve curcumin bioavailability; thus, the object of this investigation was to determine whether light exposure might also enhance curcumin efficacy in bladder cancer cell lines. RT112, UMUC3, and TCCSUP cells were preincubated with low curcumin concentrations (0.1-0.4μg/ml) and then exposed to 1.65 J/cm2visible light for 5 min. Cell growth, cell proliferation, apoptosis, cell cycle progression, and cell cycle regulating proteins along with acetylation of histone H3 and H4 were investigated. Though curcumin alone did not alter cell proliferation or apoptosis, tumor cell growth and proliferation were strongly blocked when curcumin was combined with visible light. Curcumin-light caused the bladder cancer cells to become arrested in different cell phases: G0/G1 for RT112, G2/M for TCCSUP, and G2/M- and S-phase for UMUC3. Proteins of the Cdk-cyclin axis were diminished in RT112 after application of 0.1 and 0.4μg/ml curcumin. Cell cycling proteins were upregulated in TCCSUP and UMUC3 in the presence of 0.1μg/ml curcumin-light but were partially downregulated with 0.4μg/ml curcumin. 0.4μg/ml (but not 0.1μg/ml) curcumin-light also evoked late apoptosis in TCCSUP and UMUC3 cells. H3 and H4 acetylation was found in UMUC3 cells treated with 0.4μg/ml curcumin alone or with 0.1μg/ml curcumin-light, pointing to an epigenetic mechanism. Light exposure enhanced the antitumor potential of curcumin on bladder cancer cells but by different molecular action modes in the different cell lines. Further studies are necessary to evaluate whether intravesical curcumin application, combined with visible light, might become an innovative tool in combating bladder cancer.

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LncRNA KRAL suppresses cell growth and increases sensitivity to doxorubicin in osteosarcoma cells by sponging microRNAs-141

European Journal of Inflammation ◽

10.1177/2058739220959904 ◽

2020 ◽

Vol 18 ◽

pp. 205873922095990

Author(s):

Jingwei Cai ◽

Xiaohui Chen ◽

Fei Ma ◽

Jun Qian ◽

Ming Niu ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Growth ◽

Epithelial Mesenchymal Transition ◽

Malignant Tumors ◽

Luciferase Reporter ◽

Acquired Drug Resistance ◽

Mesenchymal Transition ◽

Downstream Target ◽

Proliferation Ability ◽

Enneking Stage

Osteosarcoma (OS) is one of the most common types of malignant tumors characterized by uncontrolled proliferation ability and acquired drug resistance. The previous study indicated that lncRNA KRAL participated in the reversal of 5-FU resistance in liver cancer, but it remains unclear whether lncRNA KRAL involved in doxorubicin (DOX) resistance of osteosarcoma. The expression of lncRNA KRAL and MicroRNAs-141 (miR-141) were detected by RT-qPCR experiment. Also, we used the plasmids transfection to construct the lncRNA KRAL overexpressed OS cell lines. Subsequently, the cell proliferation ability and the sensitivity to DOX in OS cells upon upregulating lncRNA KRAL expression were analyzed via CCK-8 and EDU assay, while western blotting experiment was performed to detect the regulatory mechanism. We found that lncRNA KRAL was downregulated in OS tissues, and the OS patients with OS patients with lower expression of lncRNA KRAL were more likely to have advanced Enneking stage, larger tumor size and distant metastasis. Subsequently, we discovered that upregulation of lncRNA KRAL could inhibit cell proliferation and increase the sensitivity to DOX of OS cells. Interestingly, the western blot results showed that over-expression of lncRNA KRAL could lead to down-expression of P-gp protein and reversal of Epithelial–mesenchymal transition (EMT) pathway. Furthermore, we identified miR-141 as the downstream target gene of lncRNA KRAL, which was further confirmed by the luciferase reporter assay. More importantly, our data demonstrated that addition of miR-141 could reverse cell proliferation and drug sensitivity of lncRNA KRAL-overexpressed OS cells. LncRNA KRAL could suppress cell growth and increases sensitivity to DOX in OS cells by sponging miR-141.

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