CN-121971465-A - Pharmaceutical composition for treating gastric cancer

Abstract

The invention opens up a brand new application field of the composition formed by the diosmin and the PD-1 inhibitor, and provides a potential effective, safe and economic new therapeutic scheme for gastric cancer patients, especially patients intolerant or resistant to traditional chemotherapy. The invention demonstrates that diosmin can effectively and specifically inhibit NUAK kinase activity and thereby inhibit the downstream Wnt/β -catenin signaling pathway. The effect is directly expressed as that the protein expression levels of key transcription factors TCF4 and LEF1 are obviously down-regulated, so that the function of the diosmin as a novel NUAK inhibitor is proved on the molecular mechanism level, and the tumor inhibition effect of the composition formed by the diosmin and the PD-1 inhibitor is obviously better than that of the PD-1 inhibitor.

Inventors

• CAO LONGLONG
• LI PING
• LIN GUANGTAN
• LI LUJIE
• ZHAO YUXUAN
• WANG CHUNGUI

Assignees

• 福建医科大学附属协和医院

Dates

Publication Date

20260505

Application Date

20260206

Claims (3)

1. 1. A pharmaceutical composition for treating gastric cancer is characterized by comprising diosmin and a PD-1 inhibitor.
2. 2. The pharmaceutical composition of claim 1, wherein said diosmin is capable of inhibiting NUAK kinase activity and thereby inhibiting the Wnt/beta-catenin signaling pathway.
3. 3. The method of claim 1, wherein said diosmin is capable of down-regulating the protein expression levels of TCF4 and LEF 1.

Description

Pharmaceutical composition for treating gastric cancer Technical Field The invention belongs to the field of medicines, and in particular relates to a pharmaceutical composition of diosmin and a PD-1 inhibitor for treating gastric cancer. Background Gastric cancer is the fifth leading cause of cancer and cancer mortality worldwide, with new cases around 100 tens of thousands of deaths worldwide up to 66 tens of thousands of cases in 2022. Because of the hidden early symptoms, about 60% of patients already have advanced diagnosis, facing serious challenges of limited treatment means and poor prognosis, and the survival rate of 5 years is only 9.1%. Although innovative therapies such as immunotherapy, targeted drugs and ADC bring hopes to some patients, gastric cancer has strong heterogeneity and drug resistance problems, and most patients still have treatment failure finally. The novel therapeutic strategy with high efficiency and low toxicity, in particular to a scheme capable of precisely targeting the specific target point of gastric cancer and overcoming the drug resistance problem, is still a great demand which is not satisfied in the current clinic. Although innovative therapies such as immunotherapy, targeted drugs, and ADC offer breakthroughs for gastric cancer treatment, these approaches still have significant limitations. Therefore, there is an urgent need in the art for a novel therapeutic strategy that can simultaneously (1) target widely expressed and critical targets in gastric cancer to expand the beneficiary population, (2) effectively overcome the drug resistance problem caused by target mutation or signal pathway redundancy, and (3) have good safety to improve the quality of life of patients. Therefore, developing a therapeutic regimen that can be widely applied to most gastric cancer patients, effectively overcomes drug resistance, and is safe is a significant technical challenge for those skilled in the art. Diosmin (Diosmin) is a natural flavonoid widely existing in citrus fruits, is a mature medicament which is marketed for many years, and is mainly used for clinically treating vascular related diseases such as venous insufficiency, hemorrhoids and the like for a long time. The pharmacological effects are mainly thought to be related to increasing venous tension. Its role in gastric cancer treatment and its combined application with existing drugs have never been revealed, and its mechanism of action against gastric cancer is also completely unknown. Disclosure of Invention The invention provides application of a diosmin and PD-1 inhibitor pharmaceutical composition in preparing medicines for treating gastric cancer, provides a novel, effective and safer medicine or method for preventing or treating gastric cancer, overcomes or relieves the defects of the existing gastric cancer treatment medicines, such as large toxic and side effects, easiness in generation of drug resistance or high cost and the like, provides brand new treatment options for gastric cancer patients, opens up the new application of diosmin and provides a brand new pharmaceutical composition for treating gastric cancer. The invention provides a pharmaceutical composition for treating gastric cancer, which comprises diosmin and a PD-1 inhibitor. Furthermore, the diosmin can inhibit NUAK kinase activity, and further inhibit Wnt/beta-catenin signal pathway. Further, the above-described diosmin is capable of down-regulating the protein expression levels of TCF4 and LEF 1. The invention applies a mature old medicine and other medicines for treating gastric cancer to completely different tumor treatment fields, and the core difficulty is not in the synthesis or production of the medicine, but in the discovery of a subversion mechanism of new use of the old medicine and the cognitive breakthrough of the cross-field. Specifically, the difficulty is as follows: The complexity of mechanism exploration, even though the antitumor activity of diosmin is observed in vivo and in vitro models, further elucidating its precise target of action and molecular mechanism (e.g., whether by affecting tumor microenvironment, activating immune response or other completely new pathways) is a complex and laborious scientific work. The beneficial effects are that: the invention opens up a brand new application field of the composition formed by the diosmin and other existing medicines, and provides a potential effective, safe and economic new treatment scheme for gastric cancer patients, especially patients intolerant or resistant to traditional chemotherapy. The invention has the remarkable development advantages of greatly shortening the period from research and development to clinical application of the medicament, remarkably reducing development risk and cost, having the remarkable advantages of less investment and quick effect, and obviously improving the effect of the diosmin pharmaceutical composition compared with the treatment effect of s