A kind of antitumor pharmaceutical composition and its application
A composition and drug technology, applied in the field of tumor treatment, can solve problems such as ignorance
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Embodiment 1
[0085] Example 1 Arctigenin Selectively Induces Necrosis of A549 Cells Deprived of Glucose
[0086] In order to simulate the nutritionally deficient microenvironment of solid tumor cells in vivo, in this example, the inventors first planted the cells in a cell culture plate containing normal culture medium, and treated the cells with PBS Wash once, and then replace the cells with glucose-free or serum-free medium.
[0087] First, the tolerance of several tumor cell lines (including HepG2, Hela, A549, H4 and HGC) to glucose deficiency was tested, and the results showed that the human lung cancer cell line A549 cell line was relatively strong in tolerance to glucose deficiency . The result is as figure 1 As shown, after 24 hours of glucose deprivation, the survival rate of A549 cells was around 60%.
[0088] Next, on A549 cells, the inventors studied the effect of arctigenin on selectively killing glucose-deficient tumor cells. The results showed that arctigenin could inhibi...
Embodiment 2
[0092] Example 2 Increased intracellular ROS level is the inducement of arctigenin causing tumor cell necrosis
[0093] In order to detect whether arctigenin kills glucose-deficient tumor cells by increasing intracellular ROS, the inventors used DCFH-DA fluorescent probe to detect intracellular ROS. DCFH-DA itself has no fluorescence and can freely pass through the cell membrane. After entering the cell, it can be hydrolyzed by intracellular esterase to generate DCFH without membrane permeability. Intracellular reactive oxygen species can oxidize non-fluorescent DCFH to generate green fluorescent DCF. Therefore, the intensity of green fluorescence can reflect the level of ROS in the cell. The inventors quantified the fluorescence intensity by flow cytometry.
[0094] The results showed that arctigenin produced 5 times more ROS levels than the control group (ie DMSOin'G+S+'medium) in the absence of glucose. However, in the absence of serum, both DMSO- or arctigenin-treated c...
Embodiment 3
[0097] Example 3 Extreme lack of intracellular ATP is the cause of tumor cell necrosis caused by arctigenin
[0098] The chemical osmosis theory holds that the electron transport chain pushes H+ across the gap between the inner mitochondrial membrane and the mitochondria, resulting in a transmembrane chemical potential difference between the inner and outer sides of the membrane, which is used by ATP synthase on the membrane to make ADP and Pi synthesize ATP . Therefore, inhibition of mitochondrial respiration is likely to impede ATP synthesis. In order to detect whether arctigenin's killing of glucose-deficient tumor cells is related to the reduction of ATP, the inventors first detected the phosphorylation level of AMPK (since AMPK is an important energy sensor for cells). The results showed that arctigenin could selectively promote the phosphorylation level of AMPK in glucose-deficient cells ( Figure 5 A).
[0099] Next, the inventors used the luciferin-luciferase system...
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