Application of caffeic acid in treatment of lung cancer

Abstract

The invention relates to application of caffeic acid sensitization PD-1 in lung cancer treatment. The caffeic acid is combined with PD-1 for treatment, so that growth and immune escape of lung cancer can be inhibited.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and in particular to application of caffeic acid in treating lung cancer. Background Art

[0002] Lung cancer is one of the most common cancers worldwide, with high morbidity and mortality. It is primarily divided into two types: small cell carcinoma (SCLC) and non-small cell carcinoma (NSCLC). Survival rates for metastatic lung cancer from NSCLC and SCLC are poor. Although multiple anticancer strategies, including surgery, chemotherapy, and radiotherapy, are used to treat lung cancer, these results remain suboptimal, and effective treatment strategies are urgently needed.

[0003] Immune checkpoint inhibitors (ICIs) restore and maintain the immune system's function against tumor cells by blocking specific signaling pathways, among which cytotoxic T cells play an important role in immune surveillance and anti-tumor responses. ICIs targeting programmed cell death 1 (PD-1) / programmed cell death ligand 1 (PD-L1) can improve the survival rate of lung cancer patients to a certain extent, but only a small number of lung cancer patients with high PD-L1 expression benefit from ICI treatment. Currently, the combination strategy of PD-L1 / PD-1 inhibitors with other therapies shows great potential in improving treatment response rates. In this study, we explored the application of caffeic acid to sensitize PD-1 in the treatment of lung cancer.

[0004] Caffeic acid, a natural polyphenolic compound, has demonstrated potential therapeutic effects in various cancer models. Its mechanisms of action include antioxidant, antiproliferative, apoptosis-inducing, migration inhibition, and reversal of multidrug resistance. For example, caffeic acid enhances the efficacy of cisplatin chemotherapy by activating the mitochondrial apoptosis pathway. Some studies have also proposed the use of caffeic acid in the treatment of autoimmune diseases, but whether it can sensitize tumors to the efficacy of PD-1 / PD-L1-targeted therapies remains unclear. Summary of the Invention

[0005] In order to solve the problems of the prior art, the present invention provides an application of caffeic acid in enhancing lung cancer immunotherapy. The technical solution is as follows:

[0006] In a first aspect, a method for enhancing immunotherapy of lung cancer using caffeic acid is provided.

[0007] Furthermore, the tumor includes lung cancer.

[0008] Furthermore, the anti-tumor therapy cooperates with PD-1 therapy.

[0009] In a second aspect, a PD-1 sensitization method for treating lung cancer is provided, characterized in that the tumor growth is inhibited.

[0010] Furthermore, the CD8+ T cell infiltration was increased.

[0011] Furthermore, the ubiquitination chain of K295 is K63.

[0012] The beneficial effect of the technical solution provided by the embodiment of the present invention is that the caffeic acid of the present invention cooperates with PD-1 treatment to inhibit the growth of lung cancer cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following briefly introduces the drawings required for use in the description of the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative work.

[0014] Figure 1 This is a graph showing the gross appearance and growth curve of tumors in a mouse model of lung cancer treated with PD-1, caffeic acid, and PD-1 combined with caffeic acid in the embodiments of the present invention.

[0015] Figure 2 This is a flow cytometry analysis of CD8+T infiltration in tumor tissue of a mouse model of lung cancer treated with PD-1, caffeic acid, and PD-1 combined with caffeic acid in an embodiment of the present invention. DETAILED DESCRIPTION

[0016] To make the objectives, technical solutions and advantages of the present invention more clear, the embodiments of the present invention will be described in further detail below with reference to the accompanying drawings.

[0017] (1) Cell culture

[0018] The mouse lung cancer cell line (Lewis) was obtained from the Stem Cell Bank of the Chinese Academy of Sciences. The cells were cultured in DMEM medium containing 10% FNS and maintained at 37°C in a humidified atmosphere of 5% CO2.

[0019] (2) Lung cancer model

[0020] Prepare cell suspension and adjust the concentration to 2×10 6 / mL. Disinfect the skin under the left armpit of a C57BL / 6 mouse with alcohol. Then, inject 50 μL of the cell suspension into the mouse's left armpit using a 1 mL syringe. Pause briefly before removing the needle.

[0021] (3) Treatment strategies

[0022] The mice were divided into a control group, a PD-1 group, a caffeic acid group, and a PD-1 combined with caffeic acid group. Drug treatment was administered 7 days after model establishment. The PD-1 group received an intraperitoneal injection of a PD-1 inhibitor at a dose of 200 μg / mouse every 3 days. The caffeic acid group received an intraperitoneal injection of caffeic acid at a dose of 40 mg / kg once daily. The PD-1 combined with caffeic acid group received an injection every 3 days and caffeic acid once daily. The control group received an IgG injection.

[0023] (4) Tumor growth curve

[0024] After drug treatment, the long and short diameters of the tumors of the model mice in each group were measured every 3 days. 2 ÷2 to calculate tumor size and draw tumor growth curve.

[0025] (5) Flow cytometry

[0026] The tumor tissue of the model mice was collected and decomposed into a single cell suspension, and the clumps and fragments were removed. The suspension was centrifuged at 400×g for 5 minutes at 4°C, and the supernatant was discarded. The pellet was resuspended in flow cytometry staining solution and the cells were counted and activated. After centrifugation, the cell concentration was adjusted, and the CD8 antibody was added for incubation and the corresponding fluorescent secondary antibody was used to amplify the signal. The cell number was detected by flow cytometry.

[0027] (6) Statistical analysis

[0028] The experiment was repeated three times independently, and the results were plotted and presented as mean ± standard deviation (SD). Statistical analysis was performed using SPSS 22.0 software (IBM, USA). Student's t-test was used to analyze statistically significant differences between two groups. One-way analysis of variance (ANOVA) was used to analyze statistically significant differences between multiple groups. The significance level was set at P value < 0.05.

[0029] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. Application of caffeic acid in anti-tumor.

2. The use according to claim 1, characterized in that The tumor includes lung cancer.

3. The use according to claim 1, characterized in that The anti-tumor treatment includes sensitizing PD-1 to treat lung cancer.

4. The use according to claim 3, characterized in that The anti-tumor effect includes inhibiting tumor growth.

5. The use according to claim 3, characterized in that The anti-tumor effect includes increasing CD8+ T immune infiltration.

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