CN-121971473-A - Application of gemcitabine combined with chemotherapeutic drug of ammonia oxygen acetic acid in enhancing tumor immunity and treating colorectal cancer

CN121971473ACN 121971473 ACN121971473 ACN 121971473ACN-121971473-A

Abstract

The application discloses an application of gemcitabine combined with a chemotherapeutic drug of ammonia oxygen acetic acid in enhancing tumor immunity and treating colorectal cancer. Experiments prove that the combination of the glycine and the gemcitabine can obviously inhibit the growth of tumors and prolong the survival time of tumor-bearing mice in a subcutaneous transplantation tumor mouse model established by colorectal cancer cell line MC38 for the first time. In vivo experiments prove that the tumor volume is obviously reduced compared with a control group after the treatment by combining the glycine and the gemcitabine, the median survival time of tumor-bearing mice is obviously prolonged, and further experiments show that the combined glycine and the gemcitabine can activate tumor immune microenvironment, particularly more CD8 + T cell tumor microenvironment infiltration is shown, and the CD8 + T cell has stronger functional effect.

Inventors

YANG HUI
YE DAN
MAO YING
Liao Yuheng
WANG HANZE
LIU HANGXIN
CHEN XI

Assignees

复旦大学附属华山医院

Dates

Publication Date: 20260505
Application Date: 20260407

Claims (4)

1. Use of gemcitabine, an ammoxyacetic acid in combination with a chemotherapeutic agent, in the manufacture of a medicament for the treatment of colorectal cancer.
2. The use according to claim 1, wherein the medicament comprises a pharmaceutically active ingredient and pharmaceutically acceptable excipients, the pharmaceutically active ingredient being glycine and gemcitabine.
3. The use according to claim 1, wherein the pharmaceutically acceptable excipients are one or more of diluents, binders, wetting agents, lubricants, disintegrants, solvents, emulsifiers, co-solvents, preservatives, pH adjusters, tonicity adjusters, surfactants, coating materials, antioxidants and buffering agents.
4. The use according to any one of claims 1 to 3, wherein the medicament is in the form of an oral or injectable formulation.

Description

Application of gemcitabine combined with chemotherapeutic drug of ammonia oxygen acetic acid in enhancing tumor immunity and treating colorectal cancer Technical Field The application relates to the technical field of biological medicines, in particular to an application of an ammoxyacetic acid combined chemotherapy drug gemcitabine in enhancing tumor immunity to treat colorectal cancer. Background Colorectal cancer (colorectal cancer, CRC) is one of the digestive system malignancies with leading morbidity and mortality worldwide, severely threatening human health and bringing a heavy social and economic burden. Currently available clinical interventions such as surgical excision, radiotherapy, chemotherapy, and molecular targeted therapies, although having achieved certain effects, some patients benefit therefrom, have significant limitations. On the one hand, some patients are already at middle and late stage at the time of diagnosis, the tumor is locally aggressive or is accompanied by distant metastasis, and complete excision is difficult to realize, on the other hand, even if normalized treatment is carried out, a considerable proportion of patients have tumor recurrence and metastasis. Therefore, the overall curative effect of colorectal cancer is not ideal, and development of a new treatment strategy is urgently needed. Therefore, the molecular mechanism of colorectal cancer occurrence and development is deeply analyzed, new treatment targets are mined, and more effective combined treatment strategies are explored, so that the method has important significance for improving the overall treatment effect and prolonging the survival of patients, and also forms one of the key directions in the current tumor research field. The classical chemotherapeutic drug Gemcitabine (Gemcitabine) belongs to deoxycytidine analogues and is widely applied to clinical treatment of various solid tumors. Gemcitabine causes DNA chain extension termination by mimicking natural nucleosides, blocks DNA synthesis and causes cell death, as well as cellular DNA damage and leakage. The damaged DNA can activate the innate immune channel cGAS-STING channel, induce the generation of type I interferon and participate in the promotion of anti-tumor immunotherapy. Clinically, gemcitabine has been used for the treatment of various tumors such as pancreatic cancer, non-small cell lung cancer, bladder cancer, breast cancer and the like, and can be used as a single drug, and is often used in combination with other chemotherapeutics (such as cisplatin) to improve the curative effect. Generally, gemcitabine, which is a classical and widely used chemotherapeutic drug, plays an important role in the treatment of various solid tumors and also provides an important basis for developing novel combination treatment strategies. Although gemcitabine has shown some efficacy in a variety of solid tumors, its therapeutic effect in colorectal cancer is relatively limited. Aminooxyacetic acid (aminooxyacetic acid, AOA) is a small molecule metabolic regulation compound known to act as a transaminase inhibitor, inhibiting the enzymatic activity of pyridoxal phosphate-dependent enzymes such as glutamic oxaloacetic transaminase (glutamic-oxalacetic transaminase, GOT) and glutamic pyruvic transaminase (glutamate-pyruvate transaminase, GPT), and thus interfering with intracellular amino acid metabolic processes. The existing research mainly focuses on the role of the ammonia oxyacetic acid in the aspects of tumor metabolism reprogramming and cell proliferation regulation, and the potential application of the ammonia oxyacetic acid in tumor immunity regulation and further enhancing gemcitabine-mediated anti-tumor curative effect has not been reported yet. Therefore, how to overcome the problem of limited therapeutic effect of gemcitabine as a chemotherapeutic drug in colorectal cancer treatment, developing a combined therapeutic strategy capable of enhancing the anti-tumor immune effect thereof becomes a technical problem to be solved in the art. Disclosure of Invention The application aims to solve the technical problem that the curative effect is limited because the continuous and effective anti-tumor immune response is difficult to induce when the chemotherapeutic drug gemcitabine is used for treating colorectal cancer, and provides the application of the glycine in enhancing tumor immune treatment response and combining with gemcitabine to treat colorectal cancer. The results of the present application demonstrate that aminooxyacetic acid enhances the anti-tumor immune response by enhancing the activation level of the cGAS-STING pathway, which in turn enhances the immune response mediated by type I interferon. In order to achieve the above purpose, the present application adopts the following technical scheme: the application provides application of gemcitabine, which is an ammonia oxygen acetic acid combined chemotherapy drug, in preparing a drug for treati