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Application of proguanil to preparation of anti-tumor drug

An anti-tumor drug, the technology of proguanil, which is applied in the field of anti-tumor drugs, can solve the problems that proguanil anti-tumor research has not been reported, and achieve the effect of inhibiting tumors and broad application prospects

Active Publication Date: 2018-05-15
HUNAN NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Previous research on proguanil often focused on the inhibition of dihydrofolate reductase and the treatment of malaria, but there is no report on the anti-tumor research of proguanil

Method used

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  • Application of proguanil to preparation of anti-tumor drug
  • Application of proguanil to preparation of anti-tumor drug
  • Application of proguanil to preparation of anti-tumor drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1 proguanil antitumor activity and cytotoxicity test

[0031] 1. Experimental materials

[0032] Human bladder cancer cell line UMUC3 was purchased from Shanghai Xingbo Biotechnology Co., Ltd.;

[0033] Human bladder cancer cell line T24 was purchased from Shanghai Xingbo Biotechnology Co., Ltd.;

[0034] Human bladder cancer cell line A549 was purchased from Shanghai Xingbo Biotechnology Co., Ltd.;

[0035] Proguanil was purchased from Sigma-Aldrich Company.

[0036] 2. Experimental methods and results

[0037] Take the human bladder cancer cell line UMUC3, human bladder cancer cell line T24 and human bladder cancer cell line A549 in the logarithmic phase, and seed the plates with 7000 cells per well, and place the inoculated culture plates in the incubator Overnight, then treated with 0 μM, 3.125 μM, 6.25 μM, 12.5 μM, 25 μM, 50 μM proguanil respectively, after the treatment was completed, put the culture plates back into the incubator for 48 hours, and ...

Embodiment 2

[0039] Example 2 Proguanil inhibits tumor cell clone test

[0040] 1. Experimental materials

[0041] 10% formalin was purchased from Sinopharm Chemical Reagent Co., Ltd.;

[0042] Crystal violet staining solution was purchased from Sigma-Aldrich Company.

[0043] 2. Experimental methods and results

[0044] The human bladder cancer cell line UMUC3, the human bladder cancer cell line T24 and the human bladder cancer cell line A549 in the logarithmic growth phase were inoculated into 24-well culture plates according to 6000 cells per well, and the inoculated culture plates were placed in Overnight in the incubator to allow the cells to adhere to the wall; then the medium in the 24-well culture plate was aspirated, and 0 μM, 0.78 μM, 1.56 μM, 3.125 μM, 6.25 μM, and 12.5 μM proguanil were given respectively. After the treatment, Put the culture plates back into the incubator to continue culturing for one week; then, fix them with 10% formalin for 20 minutes, and stain with 500 μ...

Embodiment 3

[0046] Example 3 Proguanil activates AMPK test

[0047] 1. Experimental materials

[0048] Cell lysate was purchased from Bio-Rad;

[0049] TBS buffer solution was purchased from Hyclone Company;

[0050] β-ACTIN antibody, T-4EBP1 antibody, P-4EBP1 antibody, T-70S6K antibody, P-70S6K antibody, T-Thr172-AMPK antibody and P-Thr172-AMPK antibody were purchased from Cell Signaling, Beverly, MA, USA .

[0051] 2. Experimental methods and results

[0052] Add proguanil to human bladder cancer cell line T24 and human bladder cancer cell line UMUC3 respectively to make the final concentration 0, 0.19, 0.38, 0.75, 1.5 μM. After culturing for 24 hours, aspirate the culture medium and add 300 μl of cell The lysate was shaken for 30 minutes, the cells were scraped off, centrifuged at 4°C (14000×g) for 10 minutes, and the protein was quantified by the BCA method; after the quantified protein was denatured in a water bath at 100°C for 5 minutes, 20 μg of protein was taken with a micro-s...

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Abstract

The invention discloses application of proguanil to preparation of an anti-tumor drug and application of proguanil to preparation of a drug for inhibiting primary tumor growth and / or metastatic tumorgrowth; a tumor is a malignant tumor or a benign tumor, wherein the malignant tumor comprises one or more of a bladder tumor, melanoma, mastadenoma, non-Hodgkin's lymphoma, a colorectal cancer, a pancreatic cancer, an endometrial cancer, a prostate cancer, renal carcinoma, renal cell carcinoma, a non-melanoma skin cancer, leukemia, a thyroid cancer, a lung cancer, a cervical cancer, an ovarian cancer, a testicular cancer and a central nervous system tumor; the drug is a proguanil single component or a pharmaceutical composition containing an effective dose of proguanil, a drug mixture or a molecular structure modifier. Study results show that the proguanil realizes a strong anti-cancer effect by key protein AMPK in targeting tumor cell energy metabolism, and the effect of the proguanil ontumor treatment is stronger than that of N-(4-fluorophenyl) biguanidine, metformin and other biguanidine drugs.

Description

technical field [0001] The invention relates to the field of antitumor drugs, in particular to the application of proguanil in the preparation of antitumor drugs. Background technique [0002] Cancer is a risk factor that seriously affects the health of residents. In the past decade, the burden of cancer has continued to increase worldwide. In my country, cancer deaths account for 1 / 4 of all causes of death, ranking first in death. Cancer not only brings a heavy burden to patients' families and society, but also affects public safety and social stability. [0003] Bladder cancer is one of the most common malignant tumors of the urinary system in the world. The latest statistics show that the incidence of bladder cancer ranks among the top among cancer patients in the world, and it is rising year by year. It ranks seventh among male tumors in my country. Bladder cancer is a tumor of the urinary tract, and it is heterogeneous with other cancers, and it also has its own specia...

Claims

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Application Information

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IPC IPC(8): A61K31/155A61P35/00A61P35/02A61P35/04
CPCA61K31/155
Inventor 杨小平达科鸥唐弻熙邓俊贺彩梅陶婷黄妍君苏琼丽彭美
Owner HUNAN NORMAL UNIVERSITY
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