Biomed Research International
·
2021
·
IF 3.411
Fengqin Wang,Hanzhong Zhang,Zhigang Cheng
EPHA2 is a member of the ephrin receptor tyrosine kinase family and is closely related to the malignant tumor progression. The effect of EPHA2 on OSCC is not clear. This study explored the role of EPHA2 and AKT/mTOR signaling pathways in Cal-27 cell invasion and migration. The expression of EPHA2 and EPHA4 in human OSCC and normal oral tissue was detected by immunohistochemistry. EPHA2-overexpressing and EPHA2-knockdown Cal-27 cells were established, and the cells were treated with an AKT inhibitor (MK2206) and mTOR inhibitor (RAD001). The expression of EPHA2 was detected by qRT-PCR, cell proliferation was evaluated by MTT assay, cell migration and invasion were examined by scratch and Transwell assay, and cell morphology and apoptosis were assessed by Hoechst 33258 staining. Western blot was performed to detect the expression of proteins related to AKT/mTOR signaling, cell cycle, and pseudopod invasion. EPHA2 and EPHA4 were highly expressed in clinical human OSCC. Overexpression of EPHA2 promoted the proliferation, migration, and invasion of Cal-27 cells, inhibited cell cycle blockage and apoptosis, and enhanced the activity of the AKT/mTOR signaling pathway. MK2206 (AKT inhibitor) and RAD001 (mTOR inhibitor) reversed the effect of EPHA2 overexpression on the biological behavior of Cal-27 cells. EPHA2 promotes the invasion and migration of Cal-27 human OSCC cells by enhancing the AKT/mTOR signaling pathway.
研究领域:
肿瘤学
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分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MEDICINAL CHEMISTRY RESEARCH
·
2023
·
IF 2.6
Long Xing,Yang Peilin,Chen Lin,Zhong Wen,Chen Shaofeng,Li Yanping,Lin Shijie,Tian Wei
Oral cancer severely affects the quality of life of patients, and the primary treatment is surgery, due to a lack of specific drugs. Aloe emodin, a natural product of anthraquinone, is considered a potential antitumor drug. However, it has poor water solubility and low biological activity. In this study, we designed and synthesized a novel aloe emodin–hydroxyethyl piperazine hybrid dihydrochloride ( AE-NPC ), which improved the water solubility and antitumor activity of aloe emodin in vitro. According to the results, the IC 50 value of AE-NPC on CAL-27 cancer cells was 14.4 ± 2.9 μM. The flow cytometry results showed that AE-NPC induced the production of reactive oxygen species (ROS) and apoptosis in CAL-27 cells. The spectroscopy and molecular docking results showed that AE-NPC can be well intercalated into DNA grooves. Further molecular mechanism studies revealed that AE-NPC not only regulates the expression levels of key proteins (Bax/Bcl-2, cytochrome C, cleaved caspase-9 and cleaved caspase-3) of the mitochondrial apoptotic pathway but also activates the expression levels of a key protein ( γ -H 2 AX) of the DNA damage pathway. Therefore, AE-NPC induces CAL-27 cell apoptosis via DNA damage and mitochondrial pathways. This study provides new insights into the further development of anthraquinone compounds as potential chemotherapeutic agents for oral cancer treatment.
The novel aloe emodin derivative AE-NPC induces oral cancer CAL-27 cells apoptosis through ROS production, DNA damage and mitochondrial pathways. The anthraquinone compound AE-NPC may be a potential agent for the treatment of oral cancer.
研究领域:
肿瘤学
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药理学
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化疗
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细胞生物学
·
分子生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF ORGANOMETALLIC CHEMISTRY
·
2023
·
IF 2.3
Wei Tian,Jingni Wang,Wen Zhong,Hao Huang,Mingyu Ji,Tingting Yang,Shijie Lin,Shaofeng Chen,Peilin Yang
Two new anthraquinone-organotin complexes [Ph 3 Sn(O 2 CC 14 H 7 O 2 ) · MeOH] · MeOH ( AQS01 ) and Cy 3 Sn(O 2 CC 14 H 7 O 2 ) ( AQS02 ) were synthesized and characterized by elemental analysis, IR, 1 H NMR, 13 C NMR, 119 Sn NMR, X-ray crystallography and thermo-gravimetric analysis. Incorporation of 9,10-anthraquinone with organotin successfully enhanced its anticancer activity. Interestingly, the anti-proliferative activity of AQS01 against CAL-27 cells in vitro was almost 10-fold that of mitoxantrone and 40-fold that of cisplatin. Flow cytometry showed that AQS01 could induce apoptosis and arrest cell cycle in S phase. UV–visible absorption spectrometry and molecular docking showed that AQS01 can be well embedded in the double helix of DNA. Moreover, AQS01 induced cell death by upregulating the expression level of the DNA damage protein γ -H 2 AX and activating the mitochondrial apoptotic signaling pathway (Bax/Bcl-2). Therefore, AQS01 can be used as a potential anticancer drug and has potential for further research.
研究领域:
无机化学
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有机金属化学
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癌症研究
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生物化学
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药理学
✓ 已验证
DOI
高影响因子
Pharmaceutics
·
2024
·Vol. 16
·期 9
·1130
·
IF 4.9
Xiao Li,Zhiyin Li,Yue Su,Jia Zhou,Yuxiang Li,Qianqian Zhao,Xia Yang,Leilei Shi,Lingyue Shen
In the present work, we pioneered a coordinated self-assembly approach aimed at fabricating carrier-free hybrid nanoparticles to address the inherent challenges of the anaerobic microenvironment and the oxidative resistance induced by reductive glutathione (GSH) in photodynamic therapy (PDT). In these nanoparticles, protoporphyrin IX (PP), HIF-1α inhibitor ofN, Nʹ-(2,5-Dichlorosulfonyl) cystamine KC7F2 (KC), and the cofactor Fe3+present hydrogen bond and coordination interaction. The nanoparticles exhibited efficient cellular uptake by CAL-27 cells, facilitating their accumulation in tumors by enhanced permeability and retention (EPR) effect. Under irradiation at 650 nm, the formation of cytotoxic singlet oxygen (1O2) would be enhanced by the synergy effect on the Fenton reaction of Fe3+ion and the downregulation of the HIF-1α, leading to the improved PDT efficacy both in vitro and in vivo biological studies. Our work opens a new supramolecular approach to prepare hybrid nanoparticles for effective synergy therapy with PDT against cancer cells.
研究领域:
纳米技术
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癌症治疗
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生物医学工程
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药学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）