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Combined doxorubicin medicine and application thereof

A doxorubicin and drug technology, applied in the application field of doxorubicin combination drug and preparation of antitumor drugs, can solve problems such as side effects, achieve the effect of inhibiting proliferation, inducing DNA damage and cell apoptosis, and enhancing therapeutic effect. Effect

Active Publication Date: 2019-09-27
NANJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Other antitumor drugs such as paclitaxel, camptothecin, cisplatin, etc., as well as radiotherapy also have side effects of varying degrees

Method used

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  • Combined doxorubicin medicine and application thereof
  • Combined doxorubicin medicine and application thereof
  • Combined doxorubicin medicine and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: Expression of FEN1 in two colon cancer cells and normal intestinal epithelial cells

[0027] Human colon cancer cells SW480, HCT-8 and human normal intestinal epithelial cells NCM460 were selected to culture SW480, HCT-8 and NCM460 cells respectively. When the cells grew well, the samples were collected to extract proteins, and the three kinds of cells were detected by Western blot method The expression level of FEN1 in the medium, and Vinculin was used as the internal reference of the protein expression level. The result is as figure 1 , we found that the FEN1 protein levels of colon cancer SW480 and HCT-8 cells were higher than those of normal intestinal epithelial cells NCM460, which suggested that FEN1 was related to the occurrence and development of colon cancer.

Embodiment 2

[0028] Example 2: The ability to kill cells when several different chemotherapeutic drugs are used in combination with SC13

[0029] The FEN1 inhibitor SC13 was added to SW480 and HCT-8 cells respectively, but it was not found that SC13 had a significant inhibitory effect on the growth of colon cancer cells when used alone (such as figure 2 , image 3 , Figure 4 shown).

[0030] A series of chemotherapeutic drugs were used in combination with SC13 in colon cancer SW480 cells, and CCK8 was used to detect the effects of different chemotherapeutic drugs combined with SC13 on cell proliferation. When cells were treated with drug concentration gradient, CCK8 was detected 48 hours after drug addition.

[0031] The result is as figure 2 Shown, wherein, A is the effect of camptothecin alone or camptothecin combined with SC13 on the proliferation of SW480. B is the effect of paclitaxel alone or paclitaxel combined with SC13 on the proliferation of SW480. C is the effect of car...

Embodiment 3

[0034] (1) The growth inhibitory effect of Doxorubicin combined with SC13 on SW480 cells

[0035] Through the previous screening, we found a group of very effective drug combination schemes such as the combination of doxorubicin and SC13 by seeding cells in 96-well plates through CCK8. We cultured SW480 cells in 6-well plates with the same inoculum amount per well, and treated cells with SC13 or doxorubicin alone or in combination with the two drugs. The results of cell imaging showed that the use of SC13 alone did not significantly kill the cells, but at the same concentration of doxorubicin, the killing effect on the cells after adding SC13 was significantly stronger than that of doxorubicin alone ( image 3 A). The colony formation experiment further verified that the combination of SC13 and doxorubicin had an extremely obvious inhibitory effect on cell growth and the ability to form clones ( image 3 B). image 3 C is the statistical result of clone formation.

[0036]...

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PUM

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Abstract

The invention discloses a combined doxorubicin medicine. The combined doxorubicin medicine comprises doxorubicin, an FEN1 protein inhibitor and a pharmaceutically acceptable carrier. The invention further discloses application of the combined medicine to preparation of medicines for treating cancers, especially colon cancer. Experiments prove that through combined use of the doxorubicin and the FEN1 inhibitor SC13, the therapeutic effect of the Doxorubicin can be significantly enhanced, and after the combined use, proliferation of colon cancer cells is significantly inhibited and DNA damage and cell apoptosis are induced; and more importantly, through the combined use, the anti-tumor effect in a mouse model is enhanced and the dosage and the toxic and side effects of the Doxorubicin are reduced. Therefore, combination of the doxorubicin and the FEN1 protein inhibitor has a medicinal prospect in the prevention and treatment of the colon cancer.

Description

technical field [0001] The invention belongs to biomedical technology, and in particular relates to a combined drug of doxorubicin and the application of the combined drug in the preparation of antitumor drugs. Background technique [0002] At present, the morbidity and mortality of colon cancer are very high all over the world. Surgical resection is still the most effective method for colon cancer. Chemotherapy is one of the important adjuvant treatments in the treatment. Doxorubicin (or Adriamycin) has been one of the most successful drugs in cancer chemotherapy since its discovery. It is an anthracycline antibiotic that promotes tumor cell death by inducing DNA damage. Doxorubicin has been shown to intercalate into DNA, causing abnormalities in DNA replication and transcription processes, resulting in double-strand DNA breaks (DSBs). However, Doxorubicin has toxic and side effects on the human body, which greatly limits its application in clinical treatment. [0003] D...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/704A61K31/519A61P1/00A61P35/00
CPCA61K31/704A61K31/519A61P1/00A61P35/00A61K2300/00
Inventor 郭志刚何凌峰周诗颖
Owner NANJING NORMAL UNIVERSITY
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