Osteosarcoma is a highly invasive and early metastatic tumor. At present, the toxic and side effects of chemotherapy affect the quality of life of cancer patients to varying degrees. Genipin is an ...extract of the natural medicine gardenia with various pharmacological activities.
The purpose of this study was to investigate the effect of Genipin on osteosarcoma and its potential mechanism of action.
Crystal violet staining, MTT assay and colony formation assay were used to detect the effect of genipin on the proliferation of osteosarcoma. The effects of vitexin on migration and invasion of osteosarcoma were detected by scratch healing assay and transwell assay. Hoechst staining and flow cytometry were used to detect the effect of genipin on apoptosis of osteosarcoma cells. The expression of related proteins was detected by Western blot. An orthotopic tumorigenic animal model was used to verify the effect of genipin on osteosarcoma in vivo.
The results of crystal violet staining, MTT method and colony formation method proved that genipin significantly inhibited the proliferation of osteosarcoma cells. The results of the scratch healing assay and transwell assay showed that gen significantly inhibited the migration and invasion of osteosarcoma cells. The results of Hoechst staining and flow cytometry showed that genipin significantly promoted the apoptosis of osteosarcoma cells. The results of animal experiments show that genipin has the same anti-tumor effect in vivo. Genipin may inhibit the growth of osteosarcoma through PI3K/AKT signaling.
Genipin can inhibit the growth of human osteosarcoma cells, and its mechanism may be related to the regulation of PI3K/AKT signaling pathway.
Osteosarcoma(OS) is a common primary malignant bone tumor, which mostly occurs in children and adolescents. Currently, chemotherapy drugs for the clinical treatment of OS have high side effects and ...patients are prone to chemotherapy resistance, which reduces the therapeutic effect. Therefore, the development of new therapeutic drugs is very important to reduce the toxicity and adverse reactions of drugs and improve the survival rate of patients. At present, the antitumor activity of traditional Chinese medicine monomers has received extensive attention because of its safety and efficacy. Asiatic acid (AA) is a naturally pentacyclic triterpenoids extracted from Centella asiatica. The aim of this study was to evaluate the effect and mechanism of AA on OS cells in vitro and in vivo. In vitro results showed that AA inhibited the proliferation, migration and invasion of OS cells and was able to induce apoptosis and cycle arrest. In vivo results showed that AA inhibited the growth of OS and the size of lung metastasis in nude mice. Network pharmacology, molecular docking and in vitro experiments prove that AA may play a role in the treatment of OS by inhibiting PI3K/AKT and NF-κB signaling pathways. Our study shows that AA can act on multiple targets of OS and regulate multiple pathways to intervene in the occurrence and development of OS, which may provide reference for the clinical application and development of AA.
Malignant tumor is a disease caused by the imbalance of cell growth and proliferation mechanism, which seriously threatens human health and life safety. However, side effects and drug resistance are ...the key factors that limit the efficacy of anti-tumor drugs. Therefore, it is urgent and necessary to explore and unearth natural, safe and effective chemosensitizers in tumor researches. Curcumin is the main active ingredient in Curcuma, which has anti-inflammatory, anti-inflammatory and anti-oxidation effects, and has inhibitory effects on a variety of cancers. Bibliometric analysis is a scientific and quantitative method to assess the published articles, which can help researchers to find the development trends and the research hotspots of a specific research field, providing the development of future research for researchers. This study searched the Web Science Core Collection (woscc) for publications related to curcumin and tumors from January 1, 2001 to December 31, 2021. The specific characteristics of 1707 publications were analyzed by using Microsoft Excel software, CiteSpace, Vosviewer and online analysis platform of literature metrology. China had the largest number of published articles, with 579 publications. Aggarwal BB’s articles total citations and average citations were the most. PLoS One had the largest number of publications, with 32 publications. The current research focuses on “nanoparticles”, “delivery”, “micells” and “doxorubicin”. At present, nano based drug delivery system to improve the bioavailability of curcumin and thus to treat tumors will be the focus of future research.
Bladder cancer (BC) is one of the most common malignant tumors in the urinary system. Due to the poor prognosis and high mortality rate of the disease, it is urgent to develop new drugs with high ...efficacy and low toxicity to treat BC. Echinatin (Ecn) is a bioactive natural flavonoid oflicorice that has attracted special attention for its promising anti-tumor potential. Herein, we explored the inhibitory effects of Echinatin on BC cells and probed the possible molecular mechanism. We found that Ecnin vitro inhibited the proliferation, migration, and invasion, arrested the cell cycle at the G2/M phase, and promoted apoptosis in BC cells. Besides, Ecn had no notable cytotoxicity towards human normal cells. We subsequently confirmed that Ecn restrained xenograft tumor growth and metastasis of BC cells in vivo. Mechanistically, Ecn activated the p38 signaling pathway but inactivated the Wnt/β-catenin signaling pathway, while over-expression of β-catenin and the p38 inhibitor both attenuated the inhibitory effects of Ecn on BC cells. Remarkably, Ecn combined with cisplatin (DDP) or gemcitabine (Gem) had synergistic inhibitory effects on BC cells. In summary, our results validate that Ecn inhibits the tumor growth of human BC cells via p38 and Wnt/β-catenin signaling pathways. More meaningfully, our results suggest a potential strategy to enhance DDP- or Gem-induced inhibitory effects on BC cells by combining with Ecn.
Osteosarcoma (OS) is a primary malignant tumor of bone. Chemotherapy is one of the crucial approaches to prevent its metastasis and improve prognosis. Despite continuous improvements in the clinical ...treatment of OS, tumor resistance and metastasis remain dominant clinical challenges. Macropinocytosis, a form of non-selective nutrient endocytosis, has received increasing attention as a novel target for cancer therapy, yet its role in OS cells remains obscure. Benzethonium chloride (BZN) is an FDA-approved antiseptic and bactericide with broad-spectrum anticancer effects. Here, we described that BZN suppressed the proliferation, migration, and invasion of OS cells in vitro and in vivo, but simultaneously promoted the massive accumulation of cytoplasmic vacuoles as well. Mechanistically, BZN repressed the ERK1/2 signaling pathway, and the ERK1/2 activator partially neutralized the inhibitory effect of BZN on OS cells. Subsequently, we demonstrated that vacuoles originated from macropinocytosis and indicated that OS cells might employ macropinocytosis as a compensatory survival mechanism in response to BZN. Remarkably, macropinocytosis inhibitors enhanced the anti-OS effect of BZN in vitro and in vivo. In conclusion, our results suggest that BZN may inhibit OS cells by repressing the ERK1/2 signaling pathway and propose a potential strategy to enhance the BZN-induced inhibitory effect by suppressing macropinocytosis.
•Neferine is a Chinese traditional medicine, has shown inhibitory effects in osteosarcoma.•Evaluate the inhibitory effects of Neferine in vivo and vitro.•Inhibiting tumor growth by Wnt/β-catenin and ...P38/JNK pathway.•Find an efficient and secure solution for osteosarcoma.
Osteosarcoma (OS) is one of the most common types of bone malignant tumors. Clinical commonly used therapeutic drugs of OS treatment are prone to toxic and side effects, so it is supposed to develop new drugs with low toxicity and low side effects. As a Chinese traditional medicine, Neferine(C38H44N2O6) has inhibitory effects in various tumors. In the present study, we investigated the effects of Nef on OS cells in vitro and in vivo. We found that Nef inhibited cell proliferation, reduced migration, decreased invasion, and induced cell cycle arrest of OS cells. Notably, we demonstrated that Nef had no obvious effect on proliferation and apoptosis of normal cells. Besides, Nef repressed tumor growth of OS cells in xenograft mouse model. Mechanically, we found that Nef increased the phosphorylation level of P38 and JNK and suppressed Wnt/β-Catenin signaling pathway. In summary, our research validates that Nef may inhibit the proliferation, migration, and invasion of OS and promote apoptosis possibly by activating P38/JNK and suppressing Wnt/β-Catenin signaling pathway.
With the arrival of the era of the aging population, the amount of joint arthroplasty surgery keeps rising, and the articles related to the application of tranexamic acid (TXA) in joint arthroplasty ...(we called the application of tranexamic acid in joint arthroplasty as TIA in this study) also show a blowout growth. Therefore, we conducted a bibliometric analysis of TIA-related publications to identify the main research trends and hot spots in this field in the last 20 years.
In this study, publications in the field of TIA from January 1, 2002 to December 31, 2021 were searched in the Web of Science Core Collection (WoSCC). A total of 1,013 publications were evaluated for specific characteristics with Microsoft Excel software, CiteSpace, VOSviewer, and Online Analysis Platform of Literature Metrology (http://bibliometric.com/).
A total of 1,013 TIA-related articles were included in this study, and the number of articles in this field has increased yearly over the past 20 years. The USA and China dominated in the field of TIA. The Sichuan University published the most TIA-related articles among all the institutions. Of all the authors, Professor Pei was the most productive author with 64 articles. The lack of international cooperation was a significant problem in this field during the past 20 years. Furthermore, the results of the co-citation analysis and citation bursts analysis revealed that the safety and effectiveness of TIA and the optimal use strategy were the main trends and hotspots for the current and future.
This bibliometric study reviewed the evolution trend of TIA research, and identified the countries, institutions, authors and journals that have made significant contributions to this field in the past 20 years, as well as the limitations and deficiencies in this field. In addition, this study revealed that the effectiveness and safety of TIA and the optimal use strategy was the current or future research trend and hotspot in this field.
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Osteosarcoma is a primary solid bone malignancy, and surgery + chemotherapy is the most commonly used treatment. However, chemotherapeutic drugs can cause a range of side effects. ...Casticin, a polymethoxyflavonoid, has anti-tumor therapeutic effects. This study is aim to investigate the anti-osteosarcoma activity of casticin and explore the mechanism. Crystal violet staining, MTT assay, colony formation assay, wound healing assay, transwell assay, hoechst 33,258 staining, and flow cytometry analysis were used to investigate the effects of casticin on proliferation, migration, invasion, and apoptosis of osteosarcoma cells in vitro. The intracellular Fe2+, ROS, MDA, GSH/GSSG content changes were detected using the corresponding assay kits. The mRNA sequencing + bioinformatics analysis and western blot were used to detect the possible mechanism. We found that casticin caused G2/M phase cell cycle arrest in human osteosarcoma cells, inhibited the migration and invasion, and induced cell apoptosis and ferroptosis. Mechanistic studies showed the ferroptosis pathway was enriched stronger than apoptosis. Casticin up-regulated the expression of HMOX1, LC3 and NCOA4, meanwhile it activated MAPK signaling pathways. Animal experiments proved that casticin also inhibited the growth and metastasis of osteosarcoma cell xenograft tumor in vivo. In conclusion, casticin can induce ferroptosis in osteosarcoma cells through Fe2+ overload and ROS production mediated by HMOX1 and LC3-NCOA4. This provides a new strategy for osteosarcoma treatment.
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Bladder cancer (BC) is the most common malignant tumor in urinary system. Although chemotherapy is one of the most important adjuvant treatments for BC, drug resistance, non-specific ...toxicity and severe side effects are the major obstacles to BC chemotherapy. Natural products have always been a leading resource of antitumor drug discovery, with the advantages of excellent effectiveness, low toxicity, multi-targeting potency and easy availability.
In this study, we evaluated the potential anti-tumor effect of securinine (SEC), a natural alkaloid from Securinega suffruticosa, on BC cells in vitro and in vivo, and delineated the underlying mechanism. We found that SEC inhibited the proliferation, migration and invasion, induced the apoptosis of BC cells in vitro, and retarded the xenograft tumor growth of BC cell in vivo. Notably, SEC had a promising safety profile because it presented no or low toxicity on normal cells and mice. Mechanistically, SEC inactivated Wnt/β-catenin signaling pathway while activated p38 and JNK signaling pathway. Moreover, β-catenin overexpression, the p38 inhibitor SB203580 and the JNK inhibitor SP600125 both mitigated the inhibitory effect of SEC on BC cells. Furthermore, we demonstrated a synergistic inhibitory effect of SEC and gemcitabine (GEM) on BC cells in vitro and in vivo.
Taken together, our findings suggest that SEC may exert anti-BC cell effect at least through the activation of p38 and JNK signaling pathways, and the inhibition of Wnt/β-catenin signaling pathway. More meaningfully, the findings indicate that GEM-induced BC cell killing can be enhanced by combining with SEC.
