The Effect of Hispidulin, a Flavonoid from Salvia plebeia, on Human Nasopharyngeal Carcinoma CNE-2Z Cell Proliferation, Migration, Invasion, and Apoptosis

Nasopharyngeal carcinoma (NPC) is a common malignant head and neck tumor. Drug resistance and distant metastasis are the predominant cause of treatment failure in NPC patients. Hispidulin is a flavonoid extracted from the bioassay-guided separation of the EtOH extract of Salvia plebeia with strong anti-proliferative activity in nasopharyngeal carcinoma cells (CNE-2Z). In this study, the effects of hispidulin on proliferation, invasion, migration, and apoptosis were investigated in CNE-2Z cells. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay and the colony formation assay revealed that hispidulin could inhibit CNE-2Z cell proliferation. Hispidulin (25, 50, 100 μM) also induced apoptosis in a dose-dependent manner in CNE-2Z cells. The expression of Akt was reduced, and the expression of the ratio of Bax/Bcl-2 was increased. In addition, scratch wound and transwell assays proved that hispidulin (6.25, 12.5, 25 μM) could inhibited the migration and invasion in CNE-2Z cells. The expressions of HIF-1α, MMP-9, and MMP-2 were decreased, while the MMPs inhibitor TIMP1 was enhanced by hispidulin. Moreover, hispidulin exhibited potent suppression tumor growth and low toxicity in CNE-2Z cancer-bearing mice at a dosage of 20 mg/kg/day. Thus, hispidulin appears to be a potentially effective agent for NPC treatment.

Download Full-text

Cucurbitacin B as a Chinese Medicine Monomer Inhibits Cell Proliferation, Invasion, and Migration in Nasopharyngeal Carcinoma

Journal of Nanomaterials ◽

10.1155/2021/5596780 ◽

2021 ◽

Vol 2021 ◽

pp. 1-12

Author(s):

Ning Xu ◽

Bei-Bei Zhang ◽

Meng-Zhe Yang ◽

Xian-Yu Bai ◽

Zhen-Qiang Liang ◽

...

Keyword(s):

Cell Proliferation ◽

Nasopharyngeal Carcinoma ◽

Mapk Pathway ◽

Southern China ◽

Migration And Invasion ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Dependent Manner ◽

Cucurbitacin B ◽

Central Target

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor in southern China. Cucurbitacin B (CuB) is a tetracyclic triterpene compound isolated from Cucurbitaceae plants which has anti-inflammation and antitumor properties and low toxic side effects. In this study, we use a series of wet experiments and network pharmacology analyses to explore the effects of CuB on cell proliferation, migration, invasion, and apoptosis of highly metastatic 5-8F NPC cells. The findings suggest that CuB inhibits NPC cells in a time- and dose-dependent manner and that cancer migration and invasion abilities decrease significantly after CuB treatments. Mechanistically, CuB could increase the proportion of cells in the G2/M phase and reduce it in the G0/G1 phase, leading to apoptosis. The network pharmacological analyses and wet experiments uncovered that the MAPK pathway is a central target by pathway enrichment analysis, affecting the fate of cancer cells and influencing proliferation and apoptosis. Taken together, our study reveals that CuB could effectively inhibit 5-8F NPC cell proliferation, migration, and invasion via cell cycle blockage and cell apoptosis. Collectively, we have shown that CuB is a promising anti-NPC candidate compound for future preclinical study.

Download Full-text

MiR-489-3p inhibits cell proliferation, migration, and invasion, and induces apoptosis, by targeting the BDNF-mediated PI3K/AKT pathway in glioblastoma

Open Life Sciences ◽

10.1515/biol-2020-0024 ◽

2020 ◽

Vol 15 (1) ◽

pp. 274-283

Author(s):

Bo Zheng ◽

Tao Chen

Keyword(s):

Cell Proliferation ◽

Luciferase Reporter ◽

Akt Pathway ◽

Migration And Invasion ◽

Bdnf Mrna ◽

Protein Levels ◽

Rna Immunoprecipitation ◽

Underlying Mechanisms ◽

Induced Apoptosis ◽

Protein Cell

AbstractAmong astrocyte tumors, glioblastoma (GBM) is the most malignant glioma, highly aggressive and invasive, with extremely poor prognosis. Previous research has reported that microRNAs (miRNAs) participate in the progression of many cancers. Thus, this study aimed to explore the role and the underlying mechanisms of microRNA (miR)-489-3p in GBM progression. The expression of miR-489-3p and brain-derived neurotrophic factor (BDNF) mRNA was measured by quantitative real-time polymerase chain reaction. Western blot analysis was used to detect BDNF protein and the PI3K/AKT pathway-related protein. Cell proliferation, apoptosis, migration, and invasion were analyzed using CKK-8 assay, flow cytometry, and transwell assay, respectively. The interaction between BDNF and miR-489-3p was explored by luciferase reporter assay and RNA immunoprecipitation (RIP) assay. MiR-489-3p was down-regulated and BDNF was up-regulated in GBM tissues and cells. MiR-489-3p re-expression or BDNF knockdown inhibited GBM cell proliferation, migration, and invasion, and promoted apoptosis. BDNF was a target of miR-489-3p, and BDNF up-regulation reversed the effects of miR-489-3p on GBM cells. The protein levels of p-AKT and p-PI3K were notably reduced in GBM cells by overexpression of miR-489-3p, but were rescued following BDNF up-regulation. Therefore, miR-489-3p inhibited proliferation, migration, and invasion, and induced apoptosis, by targeting the BDNF-mediated PI3K/AKT pathway in GBM, providing new strategies for clinical treatment of GBM.

Download Full-text

FOXD3 inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma through regulation of the PI3K–Akt pathway

Biochemistry and Cell Biology ◽

10.1139/bcb-2020-0011 ◽

2020 ◽

Vol 98 (6) ◽

pp. 653-660 ◽

Cited By ~ 1

Author(s):

Xiaoxing Xie ◽

Gaoyun Xiong ◽

Wenjun Chen ◽

Hongdan Fu ◽

Mingqian Li ◽

...

Keyword(s):

Cell Proliferation ◽

Nasopharyngeal Carcinoma ◽

Cell Apoptosis ◽

Inhibitory Effect ◽

Akt Pathway ◽

Migration And Invasion ◽

Inhibitory Effects ◽

Protein Levels ◽

Flow Cytometric ◽

Phosphoinositide 3 Kinase

FOXD3 has been found previously to positively regulate miR-26b, a tumor inhibitor of nasopharyngeal carcinoma (NPC). However, FOXD3’s precise function and associated mechanism of action in NPC have not yet been investigated. In this study, the expression of FOXD3 mRNA and protein was evaluated using RT-qPCR, western blotting, and immunohistochemistry. Protein levels involved in the phosphoinositide 3-kinase – protein kinase B (PI3K–Akt) pathway were assessed by western blot, and cell proliferation was determined by MTT and colony forming assays. Additionally, cell apoptosis was assessed by flow cytometric assay. Finally, the migration and invasion capabilities of the NPC cells were determined using wound healing and Transwell assays. We found that FOXD3 levels were relatively low in NPC tissue and cells, while an increase caused the inhibition of the PI3K–Akt pathway. Functional experiments found that overexpression of FOXD3 suppressed cell proliferation, migration, and invasion and enhanced cell apoptosis in NPC C6661 cells. IGF-1, an activator of the PI3K–Akt pathway, reversed the inhibitory effect of FOXD3. Furthermore, we found upregulation of the PI3K–Akt pathway and upregulation of the inhibitory effects of FOXD3 on C6661 cellular activities. In conclusion, FOXD3 negatively affected the PI3K–Akt pathway to restrain the processes involved in C6661 cell pathology. These findings further exposed the function and downstream axis of FOXD3 in NPC and displayed a promising new target for NPC therapy.

Download Full-text

Curcumol inhibits malignant biological behaviors and TMZ-resistance of glioma cells via reducing long noncoding RNA FoxD2-As1 promoted EZH2 activation

10.21203/rs.3.rs-415245/v1 ◽

2021 ◽

Author(s):

Xuyang Lv ◽

Jiangchuan Sun ◽

Linfeng Hu ◽

Ying Qian ◽

Chunlei Fan ◽

...

Keyword(s):

Cell Proliferation ◽

Noncoding Rna ◽

Glioma Cell ◽

Glioma Cells ◽

Migration And Invasion ◽

Dependent Manner ◽

Antitumor Effects ◽

Self Renewal

Abstract Background: Although curcumol has been shown to possess antitumor effects in several cancers, its effects on glioma are largely unknown. Recently, lncRNAs have been reported to play an oncogenic role through epigenetic modifications. Therefore, here, we investigated whether curcumol inhibited glioma progression by reducing FOXD2-AS1-mediated enhancer of zeste homolog 2 (EZH2) activation.Methods: MTT, colony formation, flow cytometry, Transwell, and neurosphere formation assays were used to assess cell proliferation, cell cycle, apoptosis, the percentage of CD133+ cells, the migration and invasion abilities, and the self-renewal ability. qRT-PCR, western blotting, immunofluorescence, and immunohistochemical staining were used to detect mRNA and protein levels. Isobologram analysis and methylation-specific PCR were used to analyze the effects of curcumol on TMZ resistance in glioma cells. DNA pull-down and Chip assays were employed to explore the molecular mechanism underlying the functions of curcumol in glioma cells. Tumorigenicity was determined using a xenograft formation assay. Results: Curcumol inhibited the proliferation, metastasis, self-renewal ability, and TMZ resistance of glioma cells in vitro and in vivo. FOXD2-AS1 was highly expressed in glioma cell lines, and its expression was suppressed by curcumol treatment in a dose- and time-dependent manner. The forced expression of FOXD2-AS1 abrogated the effect of curcumol on glioma cell proliferation, metastasis, self-renewal ability, and TMZ resistance. Moreover, the forced expression of FOXD2-AS1 reversed the inhibitory effect of curcumol on EZH2 activation.Conclusions: We showed for the first time that curcumol is effective in inhibiting malignant biological behaviors and TMZ-resistance of glioma cells by suppressing FOXD2-AS1-mediated EZH2 activation on anti-oncogenes. Our findings offer the possibility of exploiting curcumol as a promising therapeutic agent for glioma treatment and may provide an option for the clinical application of this natural herbal medicine.

Download Full-text

Cinobufacini from the Skin of Bufo bufo gargarizans Induces Apoptosis, Possibly via Activation of the Wnt/β-Catenin Pathway, in Human Osteosarcoma Cells

Natural Product Communications ◽

10.1177/1934578x1801300221 ◽

2018 ◽

Vol 13 (2) ◽

pp. 1934578X1801300

Author(s):

Xiu-cai Ma ◽

Hui-qiang Ding ◽

Jian-dang Shi ◽

Long Hei ◽

Ning-kui Niu ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Morphology ◽

Bufo Bufo ◽

Tunel Staining ◽

Osteosarcoma Cell ◽

Dependent Manner ◽

Bufo Gargarizans ◽

Human Osteosarcoma Cells ◽

Induced Apoptosis ◽

Related Proteins

Cinobufacini (huachansu) is a traditional Chinese medicine extracted from the skin of Bufo bufo gargarizans, which is used in clinical cancer therapy. The purpose of this study was to investigate the signaling pathways regulating cinobufacini-induced apoptosis in the osteosarcoma cell line, U2OS. We used 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay to evaluate the effects of cinobufacini on cell proliferation in U2OS cells. Changes in cell morphology and apoptosis were detected by TUNEL staining. The expression of apoptosis-related and Wnt/β-catenin pathway proteins was detected by immunofluorescence, RT-PCR, and western blot analysis. Our data indicated that cinobufacini significantly inhibited cell proliferation in a dose- and time-dependent manner. Marked changes in cell morphology and apoptosis rate were clearly observed after cinobufacini treatment. The Wnt/β-catenin pathway was activated, and β-catenin expression was positive in cells after treatment. Further, protein expression of bax was increased, whereas bcl-2 was decreased, resulting in an increased bax/bcl-2 ratio. Moreover, after cinobufacini treatment, the expression of Wnt/β-catenin pathway-related proteins was similar to controls. Taken together, our study indicates that cinobufacini can induce apoptosis in U2OS cells, likely through activating the Wnt/β-catenin pathway.

Download Full-text

MicroRNA-144 promotes cell proliferation, migration and invasion in nasopharyngeal carcinoma through repression of PTEN

Carcinogenesis ◽

10.1093/carcin/bgs346 ◽

2012 ◽

Vol 34 (2) ◽

pp. 454-463 ◽

Cited By ~ 127

Author(s):

Li-Yi Zhang ◽

Victor Ho-Fun Lee ◽

Alissa Michelle Go Wong ◽

Dora Lai-Wan Kwong ◽

Ying-Hui Zhu ◽

...

Keyword(s):

Cell Proliferation ◽

Nasopharyngeal Carcinoma ◽

Migration And Invasion

Download Full-text

AIMP2-DX2 Promotes the Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma Cells

BioMed Research International ◽

10.1155/2018/9253036 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Qingsong Cao ◽

Jie Zhang ◽

Tao Zhang

Keyword(s):

Nasopharyngeal Carcinoma ◽

Protein Expression ◽

Southern China ◽

Immunohistochemical Analysis ◽

Prognostic Indicator ◽

Trna Synthetase ◽

Migration And Invasion ◽

Induced Apoptosis

Nasopharyngeal carcinoma (NPC) is a head and neck tumor with high degree of malignancy and with high incidence especially in southern China. AIMP2-DX2, one isoform of the aminoacyl-tRNA synthetase interacting multifunctional proteins (AIMPs), is shown to be a potential target in many cancers. However, the detailed mechanisms of AIMP2-DX2 in NPC development remain to be elucidated. Here, we found that the mRNA expression level of AIMP2-DX2 was significantly increased in NPC specimens, compared with normal nasopharyngeal tissues. Microarray immunohistochemical analysis of NPC specimens and Kaplan–Meier analysis showed that patients with high AIMP2-DX2 protein expression had shorter overall survival than those with low AIMP2-DX2 level. Furthermore, mRNA and protein expression levels of AIMP2-DX2 were both increased in cultured NPC cell lines (5-8F, CNE-2Z, and CNE-1), by being compared with normal nasopharyngeal cell line NP69. Overexpression of AIMP2-DX2 remarkably promoted the cell viability, cell migration, and invasion of cultured NPC cells. Genetic knockdown of AIMP2-DX2 by shRNA lentiviruses significantly suppressed the proliferation, migration, and invasion and induced apoptosis of NPC cells. Inhibition of AIMP2-DX2 decreased the highly expressed level of matrix metalloproteinase- (MMP-) 2 and MMP-9, further suppressed proliferation, migration, and invasion in cultured NPC cells in vitro, and inhibited tumor growth in a xenograft mouse model in vivo. Taken together, these results suggest that AIMP2-DX2 plays an important role in the regulation of NPC and could be a potential therapeutic target and prognostic indicator for the treatment of NPC.

Download Full-text

Downregulation of SHCBP1 Inhibits Proliferation, Migration, and Invasion in Human Nasopharyngeal Carcinoma Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8262502 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Tian Zhang ◽

Xingchen He ◽

Guodong Yu ◽

Zhixu He

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Nasopharyngeal Carcinoma ◽

Cell Lines ◽

Sh2 Domain ◽

Migration And Invasion ◽

Migration Assay ◽

Normal Tissues ◽

Delay Cell

Background. SHC SH2 domain-binding protein 1 (SHCBP1), one of the members of Src homolog and collagen homolog (Shc) family, has been reported to be overexpressed in several malignant cancers and involved in tumor progression. However, the expression of SHCBP1 in nasopharyngeal carcinoma (NPC) remains unclear, and its clinical significance remains to be further elucidated. Methods. The expression of SHCBP1 mRNA in 35 pair samples of NPC and adjacent normal tissues of NPC was detected by RT-qPCR. The expression level of SHCBP1 protein and mRNA in the selected cells was detected by western blot and RT-qPCR, respectively. The effects of SHCBP1 on NPC in vitro were observed by MTT method, colony formation assay, apoptosis assay, cell cycle assay, wound healing assay, transwell migration assay, and transwell invasion assay. Results. SHCBP1 was highly expressed in clinical tissues and NPC cell lines, and SHCBP1 knockdown significantly inhibited NPC cell proliferation. Overexpression of SHCBP1 promoted NPC cell proliferation, migration, and invasion in NPC cell lines. Silencing SHCBP1 expression can delay cell cycle and inhibit cell apoptosis. Conclusion. Our results suggest that SHCBP1 may promote proliferation and metastasis of NPC cells, which represents that SHCBP1 may act as a new indicator for predicting the prognosis of NPC and a new target for clinical treatment.

Download Full-text

The inhibition of tumor protein p53 by microRNA-151a-3p induced cell proliferation, migration and invasion in nasopharyngeal carcinoma

Bioscience Reports ◽

10.1042/bsr20191357 ◽

2019 ◽

Vol 39 (10) ◽

Cited By ~ 3

Author(s):

Haibin Liu ◽

Yin Cheng ◽

Yaping Xu ◽

He Xu ◽

Zheng Lin ◽

...

Keyword(s):

Cell Proliferation ◽

Nasopharyngeal Carcinoma ◽

B Cell Lymphoma ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Signal Pathways ◽

P53 Expression ◽

Protein P53 ◽

Tumor Protein P53

Abstract A close relation between microRNA-151a-3p (miR-151a-3p) and nasopharyngeal carcinoma (NPC) has been reported, however, the molecular mechanism is still unclear. The aim of the present study was to explore the mechanism in the promotion of miR-151a-3p to NPC progression. The levels of miR-151-3p in several NPC cell lines were detected in order to screen an experimental cell line. MiR-151a-3p mimic and inhibitor were constructed and transfected into 5-8F cells and cell proliferation were detected by Cell Counting Kit-8 (CCK-8). The apoptosis rate, cell migration and invasion were determined by flow cytometry, wound healing and Transwell assays. The predicted target was further verified by luciferase reporter assay. Real-time quantification-PCR and Western blot were carried out for mRNA and protein level analysis. Tumor protein p53 was co-transfected to verify the functions of miR-151a-3p. The miR-151a-3p level in NPC tissues was much higher than that in adjacent tissues. After transfecting cells with miR-151a-3p mimic, the cell proliferation and patients’ survival rate were much increased, and this was accompanied by the increase in B-cell lymphoma 2 (Bcl-2) and decreases in Bax and cleaved caspase-3 (P<0.01). Moreover, the migration rate and number of invaded cells were also remarkably increased, however, the miR-151a-3p inhibitor had opposite effects on the 5-8F cells. Noticeably, p53 was revealed as a potential target of miR-151a-3p. Co-transfection of P53 could partially reverse the promotive effects of miR-151a-3p on NPC cell progression. Our data indicated that blocking p53 expression and mediated signal pathways contribute to the positive effects of miR-151a-3p on NPC cell proliferation, migration and invasion.

Download Full-text

USP44 hypermethylation promotes cell proliferation and metastasis in breast cancer

Future Oncology ◽

10.2217/fon-2020-0415 ◽

2020 ◽

Author(s):

Xin Chen ◽

Xiaotang Wu ◽

Wen Lei

Keyword(s):

Breast Cancer ◽

Cell Proliferation ◽

Cancer Progression ◽

Migration And Invasion ◽

Expression Levels ◽

Cell Behaviors ◽

Specific Pcr ◽

Proliferation And Metastasis ◽

Induced Apoptosis

Aim: The methylation and expression levels of USP44 in breast cancer were investigated and their effects on tumor cells were researched. Materials & Methods: Bioinformatics was employed to identify the target gene from TCGA database. Sodium bisulfite and decitabine were used for DNA modification and demethylation, and methylation-specific PCR and reverse transcriptase PCR were performed to assess USP44 methylation and expression levels. Tumor cell behaviors were assayed via several in vitro experiments. Results: USP44 was hypermethylated, which caused its poor expression in breast cancer, whereas its overexpression significantly suppressed cancer cell proliferation, migration and invasion and induced apoptosis. Conclusion: USP44 negatively functions in cancer progression upon overexpression, indicating its potential as a therapeutic target for clinical treatment of breast cancer.

Download Full-text