Abstract
Glioma is the most common brain tumor and is characterized by high mortality rates, high recurrence rates, and short survival time. Migration and invasion are the basic features of gliomas. Thus, inhibition of migration and invasion may be beneficial for the treatment of patients with glioma. Due to its antitumor activity and chemical reactivity, fraxetin has attracted extensive interest and has been proven to be an effective antitumor agent in various cancer types. However, currently, the potential effects of fraxetin on glioma have not been investigated. Here, we demonstrate that fraxetin can inhibit the proliferation, invasion, and migration of glioma and induce apoptosis of glioma cells in vitro and in vivo. Therefore, these findings establish fraxetin as a drug candidate for glioma treatment. Furthermore, fraxetin was able to effectively inhibit the JAK2/STAT3 signaling in glioma. In summary, our results show that fraxetin inhibits proliferation, invasion, and migration of glioma by inhibiting JAK2/STAT3 signaling and inducing apoptosis of glioma cells. The present study provides a solid basis for the development of new glioma therapies.
Highlights
The most common primary malignant brain tumor, is characterized by high mortality rates, high recurrence rates, and short survival time of patients [1, 2]. e median survival time for patients diagnosed with glioma is less than 16 months, even though surgical resection combined with chemotherapy and radiotherapy is widely used to treat glioma [3, 4]. us, there is an urgent need to find new strategies for glioma treatment
Activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade is correlated with diverse cancer types, including pancreatic cancer, hepatocellular carcinoma, and glioma [5, 6]. is pathway is involved in various cellular processes, such as cellular differentiation, proliferation, migration, and apoptosis in mammals [7]. us, treatment targeting the JAK/
Our results suggested that fraxetin inhibits the proliferation, invasion, and migration of glioma and induces glioma cells apoptosis by suppressing activation of JAK2/STAT3 signaling pathway. us, fraxetin may be a promising candidate for the treatment of glioma
Summary
The most common primary malignant brain tumor, is characterized by high mortality rates, high recurrence rates, and short survival time of patients [1, 2]. e median survival time for patients diagnosed with glioma is less than 16 months, even though surgical resection combined with chemotherapy and radiotherapy is widely used to treat glioma [3, 4]. us, there is an urgent need to find new strategies for glioma treatment.Activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade is correlated with diverse cancer types, including pancreatic cancer, hepatocellular carcinoma, and glioma [5, 6]. is pathway is involved in various cellular processes, such as cellular differentiation, proliferation, migration, and apoptosis in mammals [7]. us, treatment targeting the JAK/STAT signaling pathway may be beneficial for cancer patients, through inhibiting the growth of tumor and by inducing apoptosis of cancer cells [8]. The most common primary malignant brain tumor, is characterized by high mortality rates, high recurrence rates, and short survival time of patients [1, 2]. Activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling cascade is correlated with diverse cancer types, including pancreatic cancer, hepatocellular carcinoma, and glioma [5, 6]. STAT signaling pathway may be beneficial for cancer patients, through inhibiting the growth of tumor and by inducing apoptosis of cancer cells [8]. Studies have shown that fraxetin can inhibit tumor growth and metastasis in various types of cancer, including lung cancer, breast cancer, and osteosarcoma [12]. Fraxetin can inhibit the proliferation of non-small-cell lung cancer cells by preventing activation of STAT3 [13]. Considering the observed overactivation of JAK2/STAT3 in glioma [14], we speculated that fraxetin might have an inhibitory effect on glioma development via suppressing JAK2/STAT3 activity
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