intratibial-osteosarcoma-cell-injection-to-generate-orthotopic

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models

Osteosarcoma is the most common primary bone cancer in children and adolescents, with lungs as the most common metastatic site. The five-year survival ...

establishment-patient-derived-xenograft-mouse-model-with-human

Establishment of Patient-Derived Xenograft Mouse Model with Human Osteosarcoma Tissues

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents. Despite the development of new treatment plans in recent years, ...

rna-fluorescence-situ-hybridization-for-long-non-coding-rna

RNA Fluorescence <em>In Situ</em> Hybridization for Long Non-Coding RNA Localization in Human Osteosarcoma Cells

The important roles of long non-coding RNAs (lncRNAs) in cancer have been studied, such as regulating the proliferation, epithelial-mesenchymal transition ...

intra-cardiac-injection-human-prostate-cancer-cells-to-create-bone

Intra-Cardiac Injection of Human Prostate Cancer Cells to Create a Bone Metastasis Xenograft Mouse Model

As the most common male malignancy, prostate cancer (PC) ranks second in mortality, primarily due to a 65%-75% bone metastasis rate. Therefore, it is ...

Shanghai University of Traditional Chinese Medicine

Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education

Ministry of Education

Tubeimoside-1 (TBMS1), a triterpenoid saponin isolated from the tuber of Bolbostemma paniculatum (Maxim) Franquet, serves an universal suppressive role in multiple cancer types, including lung cancer. However, the mechanism involved in non‑small cell lung cancer (NSCLC) cells by which TBMS1 elicits its antitumor effects is not yet comple-tely understood. The present study indicated that 10 µmol/l TBMS1 significantly enhanced apoptosis and notably blocked the migration and invasion of NCI‑H1299 cells. These effects were reversed following transfection with miR‑126‑5p inhi-bitor into TBMS1‑treated NCI‑H1299 cells. Vascular endo-thelial growth factor-A (VEGF‑A) is a target gene for miR‑126‑5p. Notably, results suggested that the downregulated VEGF‑A and VEGFR‑2 in TBMS1‑treated NCI‑H1299 cells were upregulated after inhibiting miR‑126‑5p, and overexpression of VEGF‑A or VEGFR‑2 could significantly reduce apoptosis and promote the migration and invasion of TBMS1‑treated NCI‑H1299 cells. Furthermore, TBMS1 combined with TBHQ (an ERK activator) dramatically suppressed TBMS1‑induced apoptosis and stimulated TBMS1‑reduced migration and invasion in NCI‑H1299 cells, suggesting that TBMS1 inhibits the ERK signaling pathway and represses the growth and metastasis of NCI‑H1299 cells. Further study demonstrated that either inhibiting miR‑126‑5p or overexpressing VEGF‑A and VEGFR‑2 in TBMS1‑treated NCI‑H1299 cells elevated the mRNA expression levels and phosphorylation levels of MEK1, as well as ERK. To conclude, TBMS1 increases miR‑126‑5p expression, whereas overexpressing miR‑126‑5p inactivates VEGF‑A/VEGFR‑2/ERK signaling pathway, which ultimately actuates the pro‑apoptotic and anti‑metastatic effects in NCI‑H1299 cells. Therefore, the present findings provide a theoretical foundation for TBMS1 as a potential candidate in NSCLC treatment.

Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway.

Tubeimoside-1 (TBMS1) possesses broad anticancer activities, including the cytostatic and anti-angiogenesis effects in lung cancer. However, the effect of TBMS1 on the metastasis of non-small cell lung cancer (NSCLC) cells and the potential underlying mechanism remain unclear. In the present study, a cell counting kit-8 assay revealed that TBMS1 suppressed the proliferation of NCI-H1299 cells significantly, particularly following 48 h of treatment. Further studies showed that TBMS1 notably enhanced the apoptosis, and inhibited the migration and invasion of NCI-H1299 cells upon treatment for 48 h. A total of 14 NSCLC tissues and 14 normal adjacent tissues were collected, reverse transcription-quantitative polymerase chain reaction revealed decreased expression of microRNA (miR)-126-5p in NSCLC tissues compared with adjacent NSCLC tissues, which was reversed following TBMS1 administration in NCI-H1299 cells. The overexpression of miR-126-5p induced by TBMS1 was demonstrated to target and downregulate vascular endothelial growth factor (VEGF)-A. Simultaneously, the expression of VEGF-R2 was reduced notably, along with a significant declined in the phosphorylation levels of dual specificity mitogen-activated protein kinase kinase 1 and extracellular signal-regulated kinase (ERK)1/2. Overall, the aforementioned results indicated that TBMS1 inhibited the proliferation and metastasis, and promoted the apoptosis of NCI-H1299 cells, which may be mediated by overexpressing miR-126-5p, which inactivates the VEGF-A/VEGFR2/ERK signaling pathway. Therefore, TBMS1 may be a promising drug for prevention and treatment of NSCLC.

Tubeimoside-1 inhibits the proliferation and metastasis by promoting miR-126-5p expression in non-small cell lung cancer cells.

 As the leading primary bone cancer in adolescents and children, osteosarcoma patients with metastasis show a five-year-survival-rate of 20-30%, without improvement over the past 30 years. Wnt/β-catenin is important in promoting osteosarcoma development. DKK3 is a Wnt/β-catenin antagonist and predicted to have the specific binding site in 3'-UTR with miR-214-3p.  miR-214-3p and DKK3 levels were investigated in human osteosarcoma tissues and cells by RT-qPCR; the prognostic importance of DKK3 level in osteosarcoma patients was determined with Log-rank test; direct binding between DKK3 with miR-214-3p was identified with targetscan; anti-osteosarcoma mechanism of cantharidin was investigated by miR-214-3p silence/over-expression with or without cantharidin treatment, and nuclear/cytoplasmic protein assay in osteosarcoma cells.  Down-regulated DKK3 indicated poor prognosis of osteosarcoma patients. Up-regulated miR-214-3p promoted proliferation and migration, while suppressed apoptosis of osteosarcoma cells by increasing β-catenin nuclear translocation and LEF1 translation via degradation of DKK3. Cantharidin suppressed viabilities, migration and invasion, while promoted cell cycle arrest and apoptosis in 143B and U-2 OS cells via down-regulating miR-214-3p to up-regulate DKK3, thus inhibited p-GSK-3β expression, β-catenin nuclear translocation and LEF1 translation. Meanwhile, cantharidin inhibited tumor growth in xenograft-bearing mice with 143B cell injection in tibia.  miR-214-3p mediated Wnt/β-catenin/LEF1 signaling activation by targeting DKK3 to promote oncogenesis of osteosarcoma; cantharidin inhibited proliferation and metastasis of osteosarcoma cells via down-regulating miR-214-3p to up-regulate DKK3 and decrease β-catenin nuclear translocation, indicating that cantharidin may be a prospective candidate for osteosarcoma treatment by targeting miR-214-3p/DKK3/β-catenin signaling.

Cantharidin inhibits osteosarcoma proliferation and metastasis by directly targeting miR-214-3p/DKK3 axis to inactivate β-catenin nuclear translocation and LEF1 translation.

Increasing studies have revealed significant associations between  with oncogenesis and prognosis of human cancers; however, pan-cancer analysis has not been reported. Here, we explored the potential carcinogenic function and the association with clinical outcomes of  in 33 different human cancers. The results showed that  was amplified in 31 investigated cancers;  expression was significantly associated with metastasis of six different cancers and significantly associated with the survival of patients in ten different cancers; TOP2A-encoded protein was obviously upregulated in five available cancers; phosphorylated TOP2A protein at S1106 was significantly upregulated in all six available cancers. Moreover,  expression was found to be associated with the cancer-associated immune cell infiltration, including fibroblasts, Tregs, and macrophages. In addition, the Kyoto encyclopedia of genes and genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses revealed a most significant association between  with the Wnt signaling pathway and DNA conformation change. This work provides a comprehensive knowledge of  in different cancers, including carcinogenic function, prognostic values for metastasis, and clinical outcomes.

Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis.

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been widely reported in various cancers. However, the potential therapeutic targets of the Chonglou active ingredients in LUAD patients remain unknown. Here, the network pharmacology and bioinformatics were performed to analyze the associations of the clinical characteristics, immune infiltration factors and mA-related genes with the EMT-related genes associated with LUAD (EMT-LUAD related genes), and the molecular docking, STRING, GO, and KEGG enrichment for the drug targets of Chonglou active ingredients associated with EMT (EMT-LUAD-Chonglou related genes). And, cell viability analysis and cell invasion and infiltration analysis were used to confirm the theoretical basis of this study. A total of 166 EMT-LUAD related genes were identified and a multivariate Cox proportional hazards regression model with a favorable predictive accuracy was constructed. Meanwhile, the immune cell infiltration, immune cell subsets, checkpoint inhibitors and the expression of mA-related genes were significantly associated with the risk scores for EMT-LUAD related genes with independent significant prognostic value of all included LUAD patients. Furthermore, 12 EMT-LUAD-Chonglou related genes with five core drug targets were identified, which participated in LUAD development through extracellular matrix disassembly, collagen metabolic process, collagen catabolic process, extracellular matrix organization, extracellular structure organization and inflammatory response. Moreover, we found that the active ingredients of Chonglou could indeed inhibit the progression of lung adenocarcinoma cells. These results are oriented towards EMT-related genes to achieve a better understanding of the role of Chonglou and its targets in osteosarcoma development and metastasis, thus guiding future preclinical studies and facilitating clinical translation of LUAD treatment.

Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes.

PD-1 inhibitors and TKIs have been used to treat advanced osteosarcoma, but there is still a lack of intuitive data for the comparison of their efficacy. We conducted a meta-analysis to evaluate their therapeutic benefits.

A meta-analysis: the clinical value of PD-1 inhibitor or protein tyrosine kinase inhibitors in the treatment of advanced osteosarcoma.

Osteosarcoma is the most common primary bone cancer in children and adolescents with high metastatic ability.

(S)-10-Hydroxycamptothecin Inhibits EMT-evoked Osteosarcoma Cell Growth and Metastasis by Activating the HIPPO Signaling Pathway.

To investigate the synergistic effects of polyphyllin I (PPI) combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling pathway.

Polyphyllin I enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth downregulating the Wnt/β-catenin pathway.

Osteosarcoma is the most common malignant bone tumor and is frequently diagnosed in juvenile. Cellular senescence is a fundamental hallmark of osteosarcoma and plays a vital role in the initiation and progression of aging and tumorigenesis. Long non-coding RNAs (lncRNAs) are implicated in tumorigenesis. In this study, six cellular senescence-related lncRNAs with independent prognostic significance in juvenile osteosarcoma patients were identified through univariate Cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression analysis, and multivariate Cox regression analysis. Prognostic significance was further confirmed by Kaplan-Meier (KM) survival curves, co-expression interaction networks, and sankey diagrams. A prognostic model of cellular senescence-related genes in juvenile osteosarcoma patients was then constructed using multivariate Cox regression analysis based on these six genes. High- and low-risk groups were identified according to the median risk score calculated by the prognostic model. The favorable prognostic significance of this model was demonstrated through survival curves, receiver operating characteristic (ROC) curves, distribution scatter plots and lncRNA expression heatmaps. Furthermore, cellular senescence-related lncRNAs were validated by enrichment analysis, immunological correlation analysis, mA correlation analysis, and drug sensitivity correlation analysis. These findings are important for improving the prognosis of juvenile osteosarcoma patients and understanding the mechanisms underlying cellular senescence in juvenile osteosarcoma development.

Cellular Senescence-Related Long Non-coding RNA Signatures Predict Prognosis in Juvenile Osteosarcoma.

 Osteosarcoma is a highly aggressive primary bone tumor that predominantly affects pediatric and adolescent populations. This study aims to explore the therapeutic potential and underlying mechanisms of melittin in treating osteosarcoma both  and .  Two osteosarcoma cell lines, namely 143B and U-2 OS, were utilized to assess the impact of melittin on cellular proliferation, apoptosis, and cell cycle progression. The effect of melittin on cell viability was evaluated using the CCK-8 assay. Flow cytometry was employed to assess apoptosis and cell cycle progression, while Western blotting analyzed the expression of key proteins, including Cdc-2, c-Myc, and ꞵ-catenin. Specifically, we employed small interfering RNA (siRNA) to selectively knock down the expression of β-catenin in two osteosarcoma cell lines. In  studies, tumor growth in nude mice was evaluated through measurements of tumor weight, volume. Additionally, immunohistochemical analysis was performed to assess Ki-67 and active ꞵ-catenin expression in tumor tissues.  Melittin induced apoptosis in 143B and U-2 OS osteosarcoma cells in a concentration-dependent manner and caused S-phase cell cycle arrest as the drug concentration increased. Mechanistic investigations revealed that melittin's efficacy was associated with the inactivation of the Wnt/ꞵ-catenin signaling pathway. Specifically, melittin treatment reduced the expression of phosphorylated glycogen synthase kinase-3 beta (p-GSK-3ꞵ) and active ꞵ-catenin. Notably, silencing β-catenin in 143B and U-2 OS osteosarcoma cells significantly enhanced the anti-proliferative and pro-apoptotic effects of melittin. This was evidenced by reduced cell viability and increased apoptosis, thereby further confirming that the anti-tumor efficacy of melittin is dependent on the inhibition of the Wnt/β-catenin signaling pathway.  studies confirmed that melittin significantly inhibited the growth of subcutaneously implanted tumors in nude mice. This inhibition was further supported by Ki-67 analyse and H&E staining, while immunohistochemical analysis revealed an obvious reduction in active ꞵ-catenin expression.  Our results offer deeper mechanistic insights into the inhibitory impact of melittin on osteosarcoma progression, at least in part by suppressing the Wnt/β-catenin signaling pathway. We expand upon previous research by providing more comprehensive and robust evidences that underscore the potential of melittin as a viable and safe therapeutic agent for osteosarcoma.

ArticleTotal : 4	Year
Publication title Cited by 4	2021
Publication title Cited by 2	2024
Publication title Cited by 4	2023
Publication title Cited by 4	2022

Article	Year
Antitumor effects of Tubeimoside-1 in NCI-H1299 cells are mediated by microRNA-126-5p-induced inactivation of VEGF-A/VEGFR-2/ERK signaling pathway. Molecular medicine reports\| PubMed ID: 29363720	2018
Tubeimoside-1 inhibits the proliferation and metastasis by promoting miR-126-5p expression in non-small cell lung cancer cells. Oncology letters\| PubMed ID: 30127904	2018
Cantharidin inhibits osteosarcoma proliferation and metastasis by directly targeting miR-214-3p/DKK3 axis to inactivate β-catenin nuclear translocation and LEF1 translation. International journal of biological sciences\| PubMed ID: 34326690	2021
Oncogenetic Function and Prognostic Value of DNA Topoisomerase II Alpha in Human Malignances: A Pan-Cancer Analysis. Frontiers in genetics\| PubMed ID: 35873470	2022
Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes. Frontiers in genetics\| PubMed ID: 36824434	2023
A meta-analysis: the clinical value of PD-1 inhibitor or protein tyrosine kinase inhibitors in the treatment of advanced osteosarcoma. Frontiers in oncology\| PubMed ID: 37377920	2023
(S)-10-Hydroxycamptothecin Inhibits EMT-evoked Osteosarcoma Cell Growth and Metastasis by Activating the HIPPO Signaling Pathway. Combinatorial chemistry & high throughput screening\| PubMed ID: 38369725	2024
Polyphyllin I enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth downregulating the Wnt/β-catenin pathway. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan\| PubMed ID: 38504531	2024
Cellular Senescence-Related Long Non-coding RNA Signatures Predict Prognosis in Juvenile Osteosarcoma. Phenomics (Cham, Switzerland)\| PubMed ID: 39723224	2024
Melittin inhibits osteosarcoma growth and by inactivating the Wnt/β-catenin signaling pathway. Journal of Cancer\| PubMed ID: 40969387	2025

Xingyuan Sun

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