Application of NR2A receptor inhibitors in the preparation of drugs for treating pancreatic cancer

Abstract

The present invention belongs to the field of biomedicine, and specifically relates to the use of NR2A receptor inhibitors in the preparation of drugs for treating pancreatic cancer. The present invention shows that glutamate derived from pancreatic cancer cells activates Schwann cells via NR2A receptors, upregulating Schwann cell activation markers GFAP, S100 and p75 NTR The study found that PEAQX, an NR2A receptor inhibitor, could inhibit the migration and proliferation of Schwann cells. Furthermore, a pancreatic cancer sciatic nerve invasion model was established, and the results showed that PEAQX could maintain the body weight of nude mice, improve sciatic nerve function scores and functional indexes, and reduce the length of sciatic nerve invasion, indicating that PEAQX can inhibit the peripheral nerve invasion of pancreatic cancer cells. Therefore, NR2A receptor inhibitors could be used as drugs to inhibit pancreatic cancer neural metastasis.

Description

Technical Field

[0001] The present invention belongs to the field of biomedicine, and particularly relates to the use of an NR2A receptor inhibitor in the preparation of a drug for treating pancreatic cancer. Background Art

[0002] Pancreatic cancer (PC) is a malignant tumor that originates from the pancreatic ductal epithelium and acinar cells and is known in the medical community as the "king of cancers." Despite continuous improvements in various treatments in recent years, pancreatic cancer remains a common disease due to its low 5-year survival rate and high risk of recurrence and metastasis after surgery. A major pathological feature of pancreatic cancer is perineural invasion (PNI), through which the tumor can metastasize along nerve fibers. Pancreatic tissue is rich in neural tissue, and this anatomical characteristic determines its high susceptibility to perineural invasion. Pancreatic cancer has the highest incidence of PNI of all cancer types, at approximately 70%-100%. Almost all pancreatic cancer patients experience PNI. PNI is closely associated with pancreatic cancer recurrence, pain, and poor prognosis.

[0003] Schwann cells (SCs), glial cells surrounding the surface of peripheral nerve fibers, play an important role in the tumor microenvironment, especially in neural infiltration. In general, Schwann cells affect tumor development and neural infiltration by mediating matrix remodeling, regulating inflammatory responses and immune cell infiltration through a variety of paracrine cytokines. Schwann cells are generally in a quiescent state. Various tumor stromal cells can secrete LIF (IL6-related stem cell promoting factor) to activate Schwann cells, promote Schwann cell growth and migration, and change the neural components of the tumor stromal matrix, including increased nerve density and excessive nerve proliferation. However, there are currently no target therapeutic drugs that inhibit the peripheral neural infiltration of pancreatic cancer by targeting key molecules for Schwann cell activation.

[0004] Therefore, there is an urgent need to develop drugs that inhibit pancreatic cancer neural metastasis in order to prolong patient survival. Summary of the Invention

[0005] In order to solve the above technical problems, NR2A receptor inhibitors are used in the preparation of drugs for treating pancreatic cancer.

[0006] The present invention provides the use of an NR2A receptor inhibitor in the preparation of a drug for treating pancreatic cancer, characterized in that the structural formula of the NR2A receptor inhibitor is shown in any one or more of the following formulas (I) to (IV);

[0007]

[0008]

[0009] Furthermore, the drug is a drug for inhibiting neural metastasis of pancreatic cancer.

[0010] Furthermore, the NR2A receptor inhibitor is used to prepare a drug for inhibiting the migration and proliferation ability of Schwann cells.

[0011] Furthermore, the NR2A receptor inhibitor is used to prepare a drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer.

[0012] Furthermore, the NR2A receptor inhibitor is used to prepare a lead drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer in a pancreatic cancer sciatic nerve infiltration mouse model.

[0013] Furthermore, the drug has an NR2A receptor inhibitor as the only active ingredient.

[0014] Furthermore, the concentration of the NR2A receptor inhibitor is 1 μM.

[0015] Furthermore, the medicine also includes pharmaceutically acceptable excipients.

[0016] Furthermore, the excipients include one or more of microcrystalline cellulose, starch, mannitol, sucrose, lactose, chitin, sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, cross-linked polyvinyl pyrrolidone, magnesium stearate, talc, glycyrrhetinic acid, hydroxypropyl methylcellulose, aspartame, and cyclamate.

[0017] Furthermore, the drug is in the form of an injection; the injection is an intraperitoneal injection preparation, an intravenous injection preparation, an intramuscular injection preparation or a subcutaneous injection preparation.

[0018] Furthermore, the injection contains an NR2A receptor inhibitor, an injection solvent and an additive; the injection solvent is one or a combination of two or more of water for injection, ethanol, propylene glycol, glycerol, isopropanol, isobutanol and polyethylene glycol; the additive is one or a combination of two or more of a pH regulator, a solubilizer, an antibacterial agent, an osmotic pressure regulator and a support agent.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] (1) The present invention shows that glutamate derived from pancreatic cancer cells can upregulate the expression of Schwann cell glutamate receptor NR2A; different concentrations of glutamate levels upregulate the expression level of Schwann cell glutamate receptor NR2A protein.

[0021] (2) The present invention also shows that glutamate can activate Schwann cells and promote their proliferation and migration, and this effect is exerted through the NR2A receptor. PEAQX, as an NR2A receptor inhibitor, can significantly inhibit the activation effect of glutamate on Schwann cells. Glutamate derived from pancreatic cancer cells activates Schwann cells through the NR2A receptor and upregulates the Schwann cell activation markers GFAP, S100 and p75. NTR The NR2A receptor can be used to inhibit pancreatic cancer neural metastasis by inhibiting the expression level of NR2A receptors, promoting the migration and proliferation of Schwann cells. The addition of PEAQX can inhibit the migration and proliferation of Schwann cells. This means that PEAQX can block the activation process of Schwann cells, thereby effectively inhibiting pancreatic cancer neural metastasis. Therefore, NR2A receptor inhibitors can be used as drugs to inhibit pancreatic cancer neural metastasis.

[0022] (3) The present invention also constructed a nude mouse pancreatic cancer sciatic nerve infiltration model. The results showed that the use of PEAQX can maintain the weight of nude mice, improve the sciatic nerve function score and functional index, and reduce the length of sciatic nerve infiltration, indicating that PEAQX can be used to treat pancreatic cancer peripheral nerve infiltration and confirming that PEAQX can inhibit pancreatic cancer neural metastasis. Therefore, NR2A receptor inhibitors can be used as drugs to inhibit pancreatic cancer neural metastasis or for preparing lead drugs that inhibit the peripheral nerve infiltration ability of pancreatic cancer in the pancreatic cancer sciatic nerve infiltration mouse model. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. 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 paying any creative work.

[0024] Figure 1 The glutamate derived from the pancreatic cancer cells of the present invention upregulates the expression of the Schwann cell glutamate receptor NR2A;

[0025] In the figure, A shows the changes in the mRNA expression levels of different types of glutamate receptors in Schwann cells after treatment with glutamate (50 μM), ns indicates no statistical significance, and * indicates P < 0.05;

[0026] B shows the changes in mRNA expression levels of different types of glutamate receptors in Schwann cells after treatment with pancreatic cancer cell conditioned medium PANC-1CM. ns indicates no statistical significance, and * indicates P < 0.05.

[0027] C shows the changes in the mRNA expression levels of different types of glutamate receptors in Schwann cells after treatment with pancreatic cancer cell conditioned medium MIAPaCa2 CM. ns indicates no statistical significance, and * indicates P < 0.05.

[0028] D is a Venn diagram plotting the intersection of differentially expressed glutamate receptors in each treatment;

[0029] E is the expression level of glutamate receptor NR2A protein encoded by GRIN2A gene after Schwann cells were treated with different concentrations of glutamate (0, 20, 50, 100 μM) verified by Western blot.

[0030] Figure 2 Glutamic acid derived from pancreatic cancer cells of the present invention activates Schwann cells and promotes their proliferation and migration;

[0031] In the figure, A is the proliferation ability of Schwann cells after treatment with glutamate (50 μM) and / or PEAQX (1 μM) using CCK-8 proliferation assay. The vertical axis represents cell viability, and the horizontal axis represents days.

[0032] B is the Transwell migration assay and scratch test to detect the migration ability of Schwann cells after treatment with glutamate (50 μM) and / or PEAQX (1 μM);

[0033] C is a Western blot assay to detect the expression of p75, an activation marker of Schwann cells, after Schwann cells were treated with glutamate (50 μM) and / or PEAQX (1 μM). NTR , GFAP, and S100 protein expression levels;

[0034] D is the CCK-8 proliferation assay to detect the proliferation capacity of Schwann cells after they were treated with pancreatic cancer cell conditioned medium (PANC-1CM and MIA PaCa2 CM) and / or PEAQX (1 μM). The vertical axis represents the cell viability.

[0035] E is a Transwell migration assay to detect the migration ability of Schwann cells after they were treated with pancreatic cancer cell conditioned medium (PANC-1CM and MIA PaCa2 CM) and / or PEAQX (1 μM);

[0036] F is Western blot detection of p75, an activation marker of Schwann cells, after Schwann cells were treated with pancreatic cancer cell conditioned medium (PANC-1CM and MIAPaCa2CM) and / or PEAQX (1 μM). NTR , GFAP, and S100 protein expression levels.

[0037] Figure 3 The in vivo study of the present invention demonstrated that PEAQX inhibited peripheral nerve invasion (PNI) of pancreatic cancer;

[0038] In the figure, A is a schematic diagram of the establishment of the sciatic nerve invasion model of pancreatic cancer in nude mice;

[0039] B is the gross image of the tumor specimen;

[0040] C is the weight growth curve of nude mice;

[0041] D is the histogram of PNI invasion length;

[0042] E is a bar graph of sciatic nerve function scores;

[0043] F is the bar graph of sciatic nerve function index. DETAILED DESCRIPTION

[0044] The present invention will be described in detail below with reference to the accompanying drawings and specific examples, but they should not be construed as limiting the present invention. Unless otherwise specified, the technical means used in the following examples are conventional means well known to those skilled in the art, and the materials, reagents, etc. used in the following examples, unless otherwise specified, can be obtained from commercial sources.

[0045] Example 1: Glutamate derived from pancreatic cancer cells upregulates the expression of Schwann cell glutamate receptor NR2A.

[0046] 1. Experimental Materials and Grouping

[0047] Experimental materials: Schwann cells sNF96.2 (purchased from American Type Culture Collection, ATCC), glutamate (G8415, Sigma), pancreatic cancer cells PANC-1, MIAPaCa2 (purchased from Shanghai Cell Bank, Chinese Academy of Sciences) derived conditioned medium (PANC-1CM, MIAPaCa2CM).

[0048] Experimental groups: (1) Schwann cells sNF96.2: control group (Control), glutamate (50μM) treatment group (L-Glutamate); (2) Schwann cells sNF96.2: control group (Control), PANC-1CM treatment group (PANC-1CM) (200,000 cells); (3) Schwann cells sNF96.2: control group (Control), MIAPaCa2 CM treatment group (MIAPaCa2 CM) (200,000 cells).

[0049] The control groups or treatment groups were co-cultured with Schwann cells for 48 h, and then the total RNA of Schwann cells was extracted. The mRNA levels of various types of glutamate receptors in Schwann cells (mGLURs receptors: GRM1, GRM2, GRM3, GRM4, GRM5, GRM6, GRM7, GRM8; AMPA receptors: GLUR1, GLUR2, GLUR3, GLUR4; NMDA receptors: GRIN1, GRIN2A, GRIN2B, GRIN2C, GRIN2D, GRIN3A, GRIN3B; kainate receptors: KA-1, KA-2) were detected by qRT-PCR.

[0050] 2. Experimental Results

[0051] like Figure 1 As shown in Figure A, compared with the control group, the mRNA expression level of GRM1 receptor in the glutamate treatment group was down-regulated, while the mRNA expression level of GRIN2A (NR2A) was up-regulated, and the mRNA expression levels of other glutamate receptors did not show significant changes. Figure 1 As shown in Figure B, after PANC-1CM treatment, the expression of GLUR1 was downregulated, while the expression of GRIN1 and GRIN2A (NR2A) was upregulated compared with the control group. Figure 1 As shown in Figure C, after treatment with MIAPaCa2 CM, GRM1 expression was downregulated, while GLUR3 and GRIN2A (NR2A) expression was upregulated compared with the control group. In summary, the mRNA expression of Schwann cell glutamate receptor GRIN2A (NR2A) was upregulated in the glutamate treatment group, PANC-1 CM treatment group, and MIAPaCa2 CM treatment group, indicating that pancreatic cancer cell-derived glutamate can upregulate the expression of Schwann cell glutamate receptor NR2A ( Figure 1 D).

[0052] Example 2: Different concentrations of glutamate levels upregulate the expression level of Schwann cell glutamate receptor NR2A protein.

[0053] 1. Experimental Materials and Grouping

[0054] Experimental materials: Schwann cell sNF96.2, glutamate.

[0055] Experimental groups: (1) Schwann cells: control group, glutamate 20 μM treatment group, glutamate 50 μM treatment group, glutamate 100 μM treatment group.

[0056] Schwann cells were cultured with different concentrations of glutamate for 48 h, and then the expression level of Schwann cell glutamate receptor NR2A was detected by Western blot.

[0057] 2. Experimental Results

[0058] like Figure 1 As shown in E, compared with the control group, the expression level of NR2A receptor protein in the glutamate treatment group was upregulated, and the higher the glutamate concentration, the higher the NR2A receptor protein level.

[0059] Example 3: Glutamate activates Schwann cells via NR2A, promoting their proliferation and migration, whereas PEAQX inhibits their proliferation and migration.

[0060] 1. Experimental Materials and Grouping

[0061] Experimental materials: Schwann cell sNF96.2, glutamate, NR2A receptor inhibitor;

[0062] The NR2A receptor inhibitor is selected from PEAQX, PPPA, PMPA or TCN201;

[0063] The structural formula of PEAQX is as follows:

[0064]

[0065] The structural formula of the PPPA is as follows:

[0066] The structural formula of the PMPA is as follows:

[0067] The structural formula of the TCN201 is as follows:

[0068]

[0069] The present invention uses PEAQX as an NR2A receptor inhibitor to illustrate the effect.

[0070] Experimental groups: (1) Schwann cells: control group (Control), glutamate (50μM) treatment group (L-Glutamate), glutamate (50μM) + 1μM PEAQX treatment group (L-Glutamate+PEAQX); 1μM PEAQX was prepared using DMSO as the solvent.

[0071] Each group was cultured with Schwann cells for 4 days, and then the proliferation ability of Schwann cells was detected by CCK-8; each group was cultured with Schwann cells for 24 hours, and then the migration ability of Schwann cells was detected by Transwell migration model and scratch test; each group was cultured with Schwann cells for 48 hours, and then the activation molecular marker p75 of Schwann cells was detected by Western blot. NTR , GFAP, and S100 protein expression levels.

[0072] 2. Experimental Results

[0073] like Figure 2 As shown in Figure A, compared with the control group, the growth rate of Schwann cells in the glutamate-treated group was faster. On the fourth day, the absorbance at 450 nm (OD 450 nm) of the Schwann cells in the glutamate-treated group was higher, indicating that glutamate significantly enhanced the proliferation of Schwann cells. However, after treatment with the NR2A receptor inhibitor PEAQX in the glutamate-treated group, the growth rate of Schwann cells decreased compared with the glutamate-treated group, and the OD 450 nm value on the fourth day was lower, indicating that PEAQX can inhibit the proliferation-promoting effect of glutamate on Schwann cells.

[0074] The present invention also uses the Transwell migration model and the scratch test to detect the activation of Schwann cells. By treating Schwann cells with PEAQX for 24 hours, the number of Schwann cells migrating in the glutamate-treated group increased compared with the control group. Glutamate treatment promoted the migration ability of Schwann cells, while the addition of PEAQX partially blocked the ability of glutamate to promote Schwann cell migration (e.g., Figure 2 B).

[0075] In addition, the present invention also explores the activation effect of glutamate on Schwann cells by detecting Schwann cell activation markers. Schwann cells were treated with PEAQX for 48 hours, and Schwann cell activation markers GFAP, S100 and p75 were detected by Western blot. NTR Compared with the control group, the expression levels of Schwann cell activation markers GFAP, S100 and p75 in the glutamate treatment group were significantly higher than those in the control group. NTR The expression levels of Schwann cell activation markers increased. When glutamate was treated with PEAQX at the same time, the expression of Schwann cell activation markers decreased, indicating that glutamate significantly upregulated the expression of Schwann cell activation markers GFAP, S100 and p75. NTR expression, an effect that could be attenuated by PEAQX inhibitors (e.g. Figure 2 C).

[0076] In summary, glutamate can activate Schwann cells and promote their proliferation and migration, and this effect is exerted through the NR2A receptor. PEAQX, as an NR2A receptor inhibitor, can significantly inhibit the activation effect of glutamate on Schwann cells.

[0077] Example 4: Glutamate derived from pancreatic cancer cells activates Schwann cells and promotes their proliferation and migration, whereas PEAQX inhibits their proliferation and migration.

[0078] 1. Experimental Materials and Grouping

[0079] Experimental materials: Schwann cells sNF96.2, PANC-1 CM, MIAPaCa2 CM, NR2A receptor inhibitor, DMEM culture medium; the NR2A receptor inhibitor is selected from PEAQX, PPPA, PMPA or TCN201, and the structure of each is the same as that in Example 3.

[0080] The effects of PEAQX as an NR2A receptor inhibitor were demonstrated.

[0081] Experimental groups: (1) Schwann cells: control group (DMEM), PANC-1CM treatment group (200,000 cells), PANC-1CM (200,000 cells) + PEAQX (1 μM) treatment group; (2) Schwann cells: control group (DMEM), MIAPaCa2 CM (200,000 cells) treatment group, MIAPaCa2 CM (200,000 cells) + PEAQX (1 μM) treatment group; 1 μM PEAQX was prepared using DMSO as the solvent.

[0082] Each group was co-cultured with Schwann cells for 72 hours, and then the cell survival rate of Schwann cells was detected by CCK-8; each group was co-cultured with Schwann cells for 24 hours, and then the migration ability of Schwann cells was detected by Transwell migration model; each group was co-cultured with Schwann cells for 48 hours, and then the expression of Schwann cell activation molecular marker p75 was detected by WB. NTR , GFAP and S100 protein expression levels.

[0083] 2. Experimental Results

[0084] like Figure 2 As shown in Figure D, compared with the control group, the absorbance of Schwann cells in the PANC-1 CM-treated group and the MIAPaCa2 CM-treated group at a wavelength of 450 nm was enhanced, while the OD 450 nm of Schwann cells in the PEAQX-treated group was decreased, indicating that the conditioned medium derived from pancreatic cancer cells PANC-1 and MIAPaCa2 enhanced the proliferation ability of Schwann cells, and this effect could be inhibited by PEAQX.

[0085] The migration ability of Schwann cells was further tested using the Transwell migration model to explore the activation of Schwann cells. Figure 2As shown in Figure E, compared with the control group, the number of Schwann cells that migrated increased in the PANC-1 CM-treated group and the MIAPaCa2 CM-treated group, while under the action of PEAQX, the number of Schwann cells that migrated decreased. The above results indicate that the conditioned medium derived from pancreatic cancer cells PANC-1 and MIAPaCa2 enhanced the proliferation and migration ability of Schwann cells, while PEAQX could inhibit this effect, indicating that glutamate derived from pancreatic cancer cells significantly enhanced the proliferation and migration ability of Schwann cells.

[0086] In addition, the expression of Schwann cell activation markers was detected by Western blot. Compared with the control group, the PANC-1CM-treated group and the MIAPaCa2CM-treated group upregulated the expression of GFAP, S100 and p75 in Schwann cells. NTR , while the addition of PEAQX could inhibit this effect ( Figure 2 F).

[0087] In summary, pancreatic cancer cell-derived glutamate activates Schwann cells via NR2A receptors and upregulates Schwann cell activation markers GFAP, S100, and p75. NTR The expression level of PEAQX was lowered, which promoted the migration and proliferation of Schwann cells, while the addition of PEAQX inhibited the migration and proliferation of Schwann cells, indicating that PEAQX can block the activation process of Schwann cells, thereby inhibiting the neural metastasis of pancreatic cancer.

[0088] Experimental Example 5: In vivo studies demonstrated the ability of PEAQX to inhibit peripheral nerve invasion (PNI) of pancreatic cancer.

[0089] 1. Experimental Materials and Grouping

[0090] Experimental materials: 5-week-old female nude mice weighing 15 g (purchased from the Experimental Animal Center of Sun Yat-sen University), pancreatic cancer cells MIAPaCa2, Schwann cells sNF96.2 and PEAQX.

[0091] Experimental groups: control group (Control), PEAQX-treated group (PEAQX), each group was repeated four times.

[0092] First, a suspension of pancreatic cancer cells MIAPaCa2 and Schwann cells sNF96.2 was prepared: pancreatic cancer cells MIAPaCa2 and Schwann cells sNF96.2 were cultured to the logarithmic growth phase, digested and centrifuged to obtain cell suspensions of MIA PaCa2 cells and sNF96.2, respectively. The cells were counted using a cell counting plate (CO010101, Countstar), and a cell suspension containing 10,000,000 MIAPaCa2 cells was aspirated. Separately, a cell suspension containing 1,000,000 sNF96.2 cells was aspirated. The two cell suspensions were mixed, centrifuged, and resuspended in 100 μL PBS to prepare a cell suspension containing 100,000 MIA PaCa2 cells / μL and 10,000 sNF96.2 cells / μL, and placed on ice for later use.

[0093] Establishment of a pancreatic cancer sciatic nerve invasion nude mouse model ( Figure 3 A): First, female nude mice weighing 15 grams and aged 5 weeks were selected. Before the experiment began, nude mice were weighed to determine the exact dose of 1% sodium pentobarbital (30 mg / kg) for intraperitoneal anesthesia. After anesthesia, the limbs of the nude mice were secured with adhesive tape in a prone position, and anesthesia was maintained by inhalation of 1% isoflurane (gas anesthesia). The epidermis of the surgical area was disinfected twice with iodine. The skin was then incised, exposing the right sciatic nerve up to the biceps femoris. Under a stereomicroscope, 3 μL of a cell suspension (MIAPaCa2 300,000 cells / sNF96.2 30,000 cells) was precisely injected into the neural capsule using a 10 μL microsyringe. After injection, the incision was sutured and disinfected again. Finally, gas anesthesia was discontinued, and the nude mice were placed on a 37°C thermoregulatory pad for warming and recovery. They were then randomly divided into two groups of four. Sciatic nerve function was scored weekly, and the extended length between the first and fifth toes of the hind limb was calculated to determine the sciatic nerve index.

[0094] In the third week, one group received an intraperitoneal injection of 100 μL PBS (control group), and the other group received an intraperitoneal injection of 100 μL PEAQX (10 mg / kg) (PEAQX-treated group), and the medication was continued for 5 consecutive days. The condition and activity of the nude mice were observed and weighed weekly. The sciatic nerve function index of the nude mice's lower limbs was measured, and the sciatic nerve function of the nude mice's lower limbs was scored. At the sixth week, the nude mice in each group were euthanized, and the sciatic nerves and tumors were harvested. The distance that the tumor cells migrated along the nerves was then measured, and photos of the tumors were taken.

[0095] like Figure 3 As shown in BF, compared with the PEAQX-treated group, the nude mice in the control group lost weight ( Figure 3C), sciatic nerve function score ( Figure 3 E) and functional index decreased ( Figure 3 F). PEAQX treatment group was able to reduce the tumor length compared with the control group ( Figure 3 B), maintain the body weight of nude mice, and improve the sciatic nerve function score ( Figure 3 E) and functional index ( Figure 3 F), and reduce the length of sciatic nerve invasion ( Figure 3 D), indicating that PEAQX can inhibit the peripheral nerve invasion ability of pancreatic cancer cells.

[0096] In summary, NR2A receptor inhibitors can be used to inhibit neural metastasis of pancreatic cancer cells.

[0097] Although the preferred embodiments of the present invention have been described, those skilled in the art may make additional changes and modifications to these embodiments once they have learned the basic creative concept. Therefore, the appended claims are intended to be interpreted as including the preferred embodiments and all changes and modifications that fall within the scope of the present invention.

[0098] Obviously, those skilled in the art may make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if such changes and modifications fall within the scope of the claims and their equivalents, the present invention is intended to include such changes and modifications.

Claims

1. Use of an NR2A receptor inhibitor in the preparation of a drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer, characterized in that: The structural formula of the NR2A receptor inhibitor is shown in the following formula (I); 。 2. Use of the NR2A receptor inhibitor according to claim 1 in the preparation of a drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer, characterized in that: The drug is a drug for inhibiting neural metastasis of pancreatic cancer.

3. Use of the NR2A receptor inhibitor according to claim 1 in the preparation of a drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer, characterized in that: The NR2A receptor inhibitor is used to prepare a drug for inhibiting the migration and proliferation ability of Schwann cells.

4. Use of the NR2A receptor inhibitor according to claim 1 in the preparation of a drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer, characterized in that The NR2A receptor inhibitor is used to prepare a lead drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer in a pancreatic cancer sciatic nerve infiltration mouse model.

5. Use of the NR2A receptor inhibitor according to claim 1 in the preparation of a drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer, characterized in that: The drug contains an NR2A receptor inhibitor as the only active ingredient.

6. Use of the NR2A receptor inhibitor according to claim 5 in the preparation of a drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer, characterized in that: The concentration of the NR2A receptor inhibitor was 1 μM.

7. Use of the NR2A receptor inhibitor according to claim 6 in the preparation of a drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer, characterized in that: The drug also includes pharmaceutically acceptable excipients.

8. Use of the NR2A receptor inhibitor according to claim 7 in the preparation of a drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer, characterized in that: The auxiliary materials include one or more of microcrystalline cellulose, starch, mannitol, sucrose, lactose, chitin, sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose, cross-linked polyvinyl pyrrolidone, magnesium stearate, talc, glycyrrhetinic acid, hydroxypropyl methylcellulose, aspartame, and cyclamate.

9. Use of the NR2A receptor inhibitor according to claim 8 in the preparation of a drug for inhibiting the peripheral nerve infiltration ability of pancreatic cancer, characterized in that: The drug is in the form of an intraperitoneal injection preparation, an intravenous injection preparation, an intramuscular injection preparation or a subcutaneous injection preparation.

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