Methods of treating colorectal cancer

Abstract

The invention discloses a medicine for treating colorectal cancer, the effective component of the medicine is MANCR siRNA (si-MANCR), and by administration of si-MANCR, the in-vivo proliferation capacity of colorectal cancer cells can be remarkably inhibited, and the in-vivo metastasis capacity of the colorectal cancer cells can be remarkably inhibited.

Description

Technical Field

[0001] The present invention belongs to the field of medical technology and more specifically relates to the application of MANCR siRNA (si-MANCR) in the treatment of colorectal cancer. Background Art

[0002] Colorectal cancer is the third most common malignant tumor in terms of morbidity and the second most common mortality rate worldwide. The early symptoms of colorectal cancer are hidden, and about 22% of patients have already developed distant metastasis by the time of diagnosis, losing the opportunity for radical surgery.

[0003] In metastatic colorectal cancer, systemic chemotherapy and targeted therapies are limited in effectiveness due to treatment resistance and the burden of disseminated cancer cells, resulting in a 5-year survival rate of only 14%. In recent years, the gut microbiome has garnered increasing attention, with numerous studies demonstrating its potential impact on the efficacy of cancer treatment. Fusobacterium nucleatum (Fn), an anaerobic bacterium commonly found in colorectal cancer (CRC) tissue, has been shown to be closely associated with the development, progression, and treatment of CRC. Therefore, there is an urgent need to investigate the mechanisms of CRC proliferation and metastasis and identify novel intervention targets to improve treatment outcomes.

[0004] si-MANCR is a siRNA with the following sequence: 5′-CCGAAACTTGCCATTT-3′. It was initially shown to inhibit the proliferation and metastasis of breast cancer, prostate cancer, and lung cancer cells. Currently, there are no reports on the use of si-MANCR in the prevention and treatment of colorectal cancer. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a new drug for treating colorectal cancer in view of the defects and shortcomings of existing colorectal cancer treatment drugs, which contains si-MANCR.

[0006] The purpose of the present invention is to provide the use of si-MANCR in the treatment of colorectal cancer.

[0007] Especially metastatic colorectal cancer.

[0008] The above-mentioned purpose of the present invention is achieved through the following technical solutions: The present invention studies have shown that Fn can significantly promote the tumorigenesis and metastasis ability of colorectal cancer cells in vivo, while si-MANCR can significantly weaken the enhancing effect of Fn on the tumorigenesis and metastasis ability of colorectal cancer cells in vivo, showing a good anti-tumor effect.

[0009] In the application of the si-MANCR in the preparation of drugs for treating colorectal cancer, preferably, the colorectal cancer refers to human colon cancer cells SW480 or HCT116, and the mice used are NOG-MHC I / II-2 KO mice.

[0010] In addition, it is particularly preferred that the above-mentioned drug refers to a drug that can inhibit the tumor formation and metastasis ability of colorectal cancer cells in the body.

[0011] Based on the above research, the present invention provides a drug for treating colorectal cancer, which contains si-MANCR.

[0012] Furthermore, the drug may further include a pharmaceutically acceptable carrier.

[0013] The present invention has the following beneficial effects: The present invention provides a new application of si-MANCR, namely, a drug for treating colorectal cancer, especially a drug for inhibiting the tumor formation and metastasis ability of colorectal cancer in the body, which can be used in the treatment of colorectal cancer proliferation and metastasis.

[0014] The present invention provides a new indication for the application of si-MANCR and also provides a new therapeutic drug and therapeutic approach for the treatment of colorectal cancer metastasis. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 The effect of si-MANCR on tumor formation of colorectal cancer cells in nude mice.

[0016] Figure 2 This is the effect of si-MANCR on tumor formation and metastasis of colorectal cancer cells in nude mice. DETAILED DESCRIPTION

[0017] The present invention will be further described below with reference to the accompanying drawings and specific examples, but the examples do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0018] Unless otherwise specified, the reagents and materials used in the following examples were commercially available.

[0019] Example 1 Experimental detection of colorectal cancer cell subcutaneous transplanted tumors in nude mice 1. Experimental Materials (1) Drug: si-MANCR.

[0020] (2) Colorectal cancer cells: human colon cancer cells HCT116.

[0021] 2. The nude mouse subcutaneous transplant tumor experiment was used to detect the effect of si-MANCR on the proliferation of colorectal cancer cell transplant tumors in nude mice.

[0022] The specific method is as follows: 1) Select 4-week-old, SPF-grade, uniform-weight, and qualified female NOG-MHC I / II-2 KO mice, which were housed in the SPF-grade animal facility of Tongji Medical College, Huazhong University of Science and Technology. Inject 5 × 10 6 PBMCs (200 µL) were used to reconstitute the human immune system.

[0023] 2) After 5 days, select HCT116 cells in good condition, digest with trypsin, and centrifuge to obtain 3×10 6 The cells were resuspended in 120 μl of PBS and inoculated subcutaneously into mice.

[0024] 3) On the third day after inoculation, Fusobacterium nucleatum (Fn, MOI = 100) and si-MANCR were injected subcutaneously around the tumor. The mice were divided into three groups: control group, Fn, and Fn + si-MANCR.

[0025] 4) Measure the weight of nude mice and the size of subcutaneous tumor every 7 days.

[0026] 5) After 4 weeks, the nude mice were euthanized, and the subcutaneous tumors were removed and weighed.

[0027] 3. Experimental results result Figure 1 As shown, in the subcutaneous colorectal cancer cell transplant model, after treatment with si-MANCR, the size and tumor size of the subcutaneous transplanted tumors were significantly reduced, indicating that si-MANCR can significantly inhibit the proliferation of colorectal cancer cells in vivo.

[0028] Example 2 Experimental detection of colorectal cancer cell transplanted tumors in nude mice lungs 1. Experimental Materials (1) Drug: si-MANCR.

[0029] (2) Colorectal cancer cells: human colon cancer cells HCT116.

[0030] 2. The nude mouse colorectal cancer lung transplant tumor experiment was used to detect the effect of si-MANCR on the metastasis of colorectal cancer cell transplant tumors in nude mice.

[0031] The specific method is as follows: 1) Select 4-week-old, SPF-grade, uniform-weight, and qualified female NOG-MHC I / II-2 KO mice, which were housed in the SPF-grade animal facility of Tongji Medical College, Huazhong University of Science and Technology. Inject 5 × 10 6PBMCs (200 µL) were used to reconstitute the human immune system.

[0032] 2) After 5 days, select HCT116 cells in good condition, digest with trypsin, and centrifuge to obtain 4×10 6 The cells were resuspended in 100 μl of PBS and inoculated into nude mice via the tail vein. HCT116 cells were divided into three groups: control, Fn, and Fn + si-MANCR, depending on whether they were co-cultured with Fn or si-MANCR for 48 hours.

[0033] 3) After 4 weeks, the nude mice were euthanized, and the lungs were removed, weighed, fixed with paraformaldehyde solution, and sectioned for HE staining.

[0034] (2) Experimental results result Figure 2 As shown in the colorectal cancer cell lung metastasis model, the number of lung metastases and the proportion of lung metastases were significantly reduced after si-MANCR treatment, indicating that si-MANCR can significantly inhibit the metastatic ability of colorectal cancer cells in vivo.

[0035] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be considered as equivalent replacement methods and are included in the scope of protection of the present invention.

Claims

1. Use of MANCR siRNA in preparing a drug for treating colorectal cancer, characterized in that: The sequence of the MANCR siRNA is 5′-CCGAAACTTGCCATTT-3′ 2. Use of MANCR siRNA in the preparation of a drug for inhibiting colorectal cancer lung metastasis, characterized in that the sequence of the MANCR siRNA is 5′-CCGAAACTTGCCATTT-3′.

3. The use according to any one of claims 1-2, wherein the medicine further comprises a pharmaceutically acceptable carrier, excipient, or diluent.

4. A pharmaceutical composition, characterized in that The pharmaceutical composition comprises a first active ingredient and a second active ingredient, wherein the first active ingredient is MANCR siRNA, the sequence of the MANCR siRNA is 5′-CCGAAACTTGCCATTT-3′, and the second active ingredient is a chemotherapeutic agent. The pharmaceutical composition is used to treat colorectal cancer.

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