Inhibitor for treating renal clear cell carcinoma

A technology for renal clear cell carcinoma and cells, which is applied in the field of medicine, can solve problems such as poor therapeutic effect, and achieve the effect of improving application value, increasing activity, and inhibiting growth

Pending Publication Date: 2022-07-05
中国人民解放军陆军特色医学中心
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its therapeutic effect is still not good at present, and it has important clinical significance to combine with other drugs to sensitize the effect of everolimus

Method used

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  • Inhibitor for treating renal clear cell carcinoma
  • Inhibitor for treating renal clear cell carcinoma
  • Inhibitor for treating renal clear cell carcinoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: GLUL is highly expressed in renal clear cell carcinoma (ccRCC) and is closely related to the prognosis of renal clear cell carcinoma.

[0027] Using the TCGA public database resources, we analyzed GLUL protein expression levels and copy number changes in ccRCC and paracancerous tissues to understand the important role of GLUL expression in ccRCC. At the same time, we used the ccRCC tissue microarray and follow-up database of our unit (the Chinese People's Liberation Army Army Characteristic Medical Center) to analyze the relationship between GLUL and the fuhrman classification and prognosis of ccRCC.

[0028] We analyzed the ccRCC proteomics public database of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and found that the expression level of GLUL in ccRCC primary lesions was significantly higher than that in adjacent tissues, suggesting that GLUL is related to the occurrence of ccRCC [ figure 1 A]. Using UCSC Xena (https: / / xena.ucsc.edu), we an...

Embodiment 2

[0029] Example 2: L-methionine sulfoxide imide (MSO) can inhibit the growth and proliferation of renal clear cell carcinoma cell lines in vitro at cellular and organoid levels.

[0030] The growth and proliferation of cells and organoids after MSO treatment were detected by CCK8, clone formation and organoid experiments.

[0031] For CCK8 experiments: digest 786-O cells with 0.25% trypsin, count the appropriate number of cells and resuspend in complete medium, 0.1×10 4The cells were added to the 96-well plate for culture, and the cells were cultured with CCK8 for 4 hours after the cells completely adhered to the wall the next day, and then the absorbance was measured at a wavelength of 450 nm, which was the absorbance value on the 0th day. Divided into two groups (control group DMSO 1‰, MSO group MSO 30mM), each group had 5 duplicate wells, added the corresponding medium to continue culturing, and tested the absorbance for 4 consecutive days. It can be seen that 30mM has a si...

Embodiment 3

[0034] Example 3: L-methionine sulfoxide imide (MSO) inhibits the growth and proliferation of renal clear cell carcinoma on subcutaneous inoculation and PDX models, while increasing the drug effect of everolimus

[0035] Subcutaneous inoculation of 786-O cell line and PDX model were used to detect the growth and proliferation effects of MSO on ccRCC, and the anti-tumor effect of combined everolimus.

[0036] For subcutaneous xenograft experiments, after expansion of the 786-O cell line, resuspend the cells in a 1:1 ratio of PBS: Matrigel at a cell concentration of 5x10 6 / 100μl. 4-week-old nude mice were selected, and 100 μl of cell suspension was subcutaneously injected into the back of the nude mice. When the tumor volume reached about 50-100 mm 3 given drug treatment. Experimental design Four groups (there was no significant difference in initial tumor volume among the four groups) were control group (DMSO 1‰, gavage), MSO group (10mg / kg, intraperitoneal injection), and E...

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Abstract

The invention discloses an inhibitor for treating renal clear cell carcinoma, the research result of the applicant shows that L-methionine sulfoximine (MSO for short) as a blocker of glutamine synthetase (GLUL) has the functions of obviously inhibiting the growth, proliferation and metastasis of the renal clear cell carcinoma, and a new hope is brought to the treatment of the renal clear cell carcinoma; furthermore, the L-methionine sulfoximide and the everolimus can effectively inhibit the growth and proliferation of the renal clear cell carcinoma in the animal level, and after the L-methionine sulfoximide and the everolimus are combined for use, the inhibition function on the growth and proliferation of the renal clear cell carcinoma is more excellent, and the L-methionine sulfoximide and the everolimus have great potential and can be used for treating the renal clear cell carcinoma.

Description

technical field [0001] The invention belongs to the technical field of medicine, and particularly relates to the application of an L-methionine sulfoxide imide as a drug for renal clear cell carcinoma. Background technique [0002] Clear cell renal cell carcinoma (ccRCC) is the most common pathological type of renal cell carcinoma (70%-75%). Studies have found that more than 90% of ccRCCs have VHL abnormalities, such as mutation, methylation, etc., and the inactivation of VHL (Von Hippel-Lindau) gene function is an important molecular basis for the occurrence and development of ccRCC. The greatest progress in renal cancer drug treatment in the past few decades has been drugs targeting VEGFR (vascular endothelial growth factor receptor) downstream of the VHL-HIF (hypoxia-inducible factor) pathway, such as sunitinib, sorafil Ni et al. These antiangiogenic drugs do achieve some efficacy in some metastatic renal cancers; however, these drugs often suffer from off-target effect...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/198A61P13/12A61P35/00
CPCA61K31/198A61P13/12A61P35/00
Inventor 刘秋礼江军彭松徐静兰卫华王洛夫
Owner 中国人民解放军陆军特色医学中心
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