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Application of ferroptosis inducer RSL3, and medicine for treating liver cancer

A technology for the treatment of liver cancer and ferroptosis, applied in the fields of cell biology and medicine, can solve the problems of unclear tolerance mechanism, prolonging the survival time of liver cancer patients and physical damage

Active Publication Date: 2021-06-25
DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clinical trials have found that sorafenib can prolong the survival time of patients with liver cancer and reduce the physical damage caused by chemotherapy, but there is drug resistance, and the specific resistance mechanism is not yet clear

Method used

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  • Application of ferroptosis inducer RSL3, and medicine for treating liver cancer
  • Application of ferroptosis inducer RSL3, and medicine for treating liver cancer
  • Application of ferroptosis inducer RSL3, and medicine for treating liver cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Example 1 Preparation of ferroptosis inducer RSL3, ferroptosis inhibitors Ferrostatin-1 and Liproxstatin-1 and sorafenib solution.

[0015] RSL3, Ferrostatin-1 (Fer-1), Liproxstatin-1 (Lip-1) and sorafenib were all dissolved in DMSO, and the concentration of the storage solution was 100mM. Use DMEM medium to dilute RSL3 to 0.0020, 0.0039, 0.0078, 0.0156, 0.0313, 0.0625, 0.1250, 0.2500, 0.5000, 1.0000, 2.0000μM; use DMEM medium to dilute Fer-1 and Lip-1 to 0.4μM and 0.5 μM; Dilute sorafenib to 8 μM using DMEM medium.

Embodiment 2

[0016] Example 2 RSL3 induces ferroptosis in Sorafenib-resistant liver cancer cells

[0017] HepG2 and HepG2 drug-resistant cells (the construction of HepG2 drug-resistant cells adopts the concentration gradient increasing method, HepG2 is in the DMEM medium containing volume concentration 10% FBS (fetal bovine serum), volume concentration 5% CO 2 Cultivate overnight in an incubator at 37°C in air, and add sorafenib when the cell density reaches 60-70%. The initial dose of sorafenib is 0.2 μM. After 24 hours of cultivation, wash with dPBS to remove most of the dead cells, replace the DMEM medium, and wait for the cells to After the growth was stable, the drug dose was increased to 0.3 μM, and the dose of sorafenib was increased sequentially according to the above method. After 8 months, the drug dose of sorafenib was terminated at 0.8 μM, and the construction of the HepG2 drug-resistant cell line was completed. The drug-resistant liver cancer cells were named HepG2R) with 4×10...

Embodiment 3

[0018] Example 3 RSL3 Promotes Lipid Peroxide Synthesis in Sorafenib-resistant Liver Cancer Cells

[0019] HepG2 and HepG2R cells were divided into 4 × 10 3 Cells were seeded in 20mm culture dishes, and treated with 1μM RSL3 for 1-3h, and then added 2μM 581 / 591C11 and 1 μg / mL Hoechst dye were incubated for 20 min for live cell imaging, washed once with dPBS, and cells were imaged at 20× magnification using laser confocal. Images of each dish were collected using the same instrument parameters to maximize the ability to compare results between conditions. The result is as image 3 As shown, compared with HepG2 cells, the accumulation of lipid peroxide in HepG2R cells was significantly increased after adding RSL3 for 1 h, and drug-resistant cells showed higher sensitivity to ferroptosis than non-resistant cells, which was triggered by increasing lipid oxidation. cell death.

[0020] In summary, ferroptosis inducer RSL3 treatment can increase the accumulation of lipid peroxi...

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Abstract

The invention discloses an application of a ferroptosis inducer RSL3 in treatment of sorafenib drug-resistant liver cancer, and belongs to the technical field of cytobiology and medicine. Specifically, RSL3 with different concentrations is added into HepG2 and HepG2 drug-resistant cells, the cell activity is detected by using a Cell Counting Kit-8 method, and it is found that compared with the HepG2 cells, the relative activity of the HepG2 drug-resistant cells is remarkably reduced, and the RSL3 can inhibit proliferation of liver cancer drug-resistant cells. Meanwhile, compared with the accumulation condition of lipid oxides of HepG2 and HepG2 drug-resistant cells, the lipid oxides of the HepG2 drug-resistant cells are remarkably increased after the RSL3 is added, so that ferroptosis is caused. The ferroptosis inducer RSL3 has good medicinal potential in treatment of drug-resistant tumors.

Description

technical field [0001] The invention belongs to the field of cell biology and medical technology, and specifically relates to a new method for RSL3 in treating drug-resistant liver cancer cell ferroptosis. Background technique [0002] Hepatocellular carcinoma (HCC) is one of the common malignant tumors in my country, and its incidence rate accounts for about 50% of the global total. The early symptoms of liver cancer are not obvious, and most patients are already in the middle and late stages when they are diagnosed. Due to the high prevalence, With increased multidrug resistance (MDR) and tumor cell metastasis, liver cancer remains a prevalent healthcare problem worldwide. In 2007, sorafenib was approved by the FDA as a first-line targeted drug for unresectable and advanced liver cancer. It has multi-kinase inhibitory activity to inhibit tumor angiogenesis, cell proliferation and promote tumor cell apoptosis. Clinical trials have found that sorafenib can prolong the surviv...

Claims

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Application Information

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IPC IPC(8): A61K31/437A61P35/00A61P1/16
CPCA61K31/437A61P35/00A61P1/16
Inventor 刘扬高云娜吴长清
Owner DALIAN INST OF CHEM PHYSICS CHINESE ACAD OF SCI
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