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通关藤提取物(MTE)通过增强PTEN来使PI3K/AKT/mTOR信号通路失活,从而抑制人急性T细胞白血病细胞的增殖并诱导其凋亡。

Marsdenia tenacissimae extraction (MTE) inhibits the proliferation and induces the apoptosis of human acute T cell leukemia cells through inactivating PI3K/AKT/mTOR signaling pathway via PTEN enhancement.

作者信息

Wang Ying, Chen Bingyu, Wang Zhen, Zhang Wei, Hao Ke, Chen Yu, Li Kaiqiang, Wang Tongtong, Xie Yiwei, Huang Zhihui, Tong Xiangmin

机构信息

Key Laboratory of Laboratory Medicine, Ministry of Education, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.

Department of Blood Transfusion, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, 310014, China.

出版信息

Oncotarget. 2016 Dec 13;7(50):82851-82863. doi: 10.18632/oncotarget.12654.

Abstract

Marsdenia tenacissimae extraction (MTE) as a traditional Chinese herb has long been used to treat some diseases such as tumors in China. However, the potential effectiveness of MTE in leukemia has not yet been fully understood, and the related molecular mechanism is still unknown. In the present study, we aimed to evaluate the effects of MTE on the proliferation and apoptosis of Jurkat cells (T-ALL lines) and lymphocytes from T-ALL (T-cell acute lymphoblastic leukemia) patients. Firstly, CCK8 assays and flow cytometry assays revealed that MTE dose-dependently reduced the proliferation of Jurkat cells by arresting cell cycle at S phase. Secondly, Annexin V-FITC/PI-stained flow cytometry and TUNEL staining assays showed that MTE promoted the apoptosis of Jurkat cells. Mechanistically, MTE enhanced PTEN (phosphatases and tensin homolog) level and inactivated PI3K/AKT/mTOR signaling pathway in Jurkat cells, which mediated the inhibition of cell proliferation by MTE and MTE-induced apoptosis. Finally, MTE significantly inhibited the proliferation and promoted the apoptosis of lymphocytes from T-ALL patients, compared with lymphocytes from healthy peoples. Taken together, these results reveal an unrecognized function of MTE in inhibiting the proliferation and inducing the apoptosis of T-ALL cells, and identify a pathway of PTEN/PI3K/AKT/mTOR for the effects of MTE on leukemia therapy.

摘要

通关藤提取物(MTE)作为一种传统中药,在中国长期以来一直被用于治疗某些疾病,如肿瘤。然而,MTE在白血病中的潜在疗效尚未完全明确,其相关分子机制仍不清楚。在本研究中,我们旨在评估MTE对Jurkat细胞(T-ALL细胞系)以及T-ALL(T细胞急性淋巴细胞白血病)患者淋巴细胞增殖和凋亡的影响。首先,CCK8检测和流式细胞术检测显示,MTE通过将细胞周期阻滞在S期,剂量依赖性地降低Jurkat细胞的增殖。其次,Annexin V-FITC/PI染色流式细胞术和TUNEL染色检测表明,MTE促进Jurkat细胞凋亡。机制上,MTE提高了Jurkat细胞中PTEN(磷酸酶和张力蛋白同源物)水平并使PI3K/AKT/mTOR信号通路失活,这介导了MTE对细胞增殖的抑制以及MTE诱导的凋亡。最后,与健康人淋巴细胞相比,MTE显著抑制T-ALL患者淋巴细胞的增殖并促进其凋亡。综上所述,这些结果揭示了MTE在抑制T-ALL细胞增殖和诱导其凋亡方面的一种未被认识的功能,并确定了PTEN/PI3K/AKT/mTOR通路介导MTE对白血病治疗的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c208/5347737/8f3c827a3fc2/oncotarget-07-82851-g001.jpg

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