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Application of brusatol as chemotherapeutic drug synergist

A technique for nucleoside and a chemotherapeutic agent, which is applied in the field of nucleoside as a synergist of chemotherapeutic agents to achieve the effect of increasing growth inhibition

Inactive Publication Date: 2011-06-29
SHANDONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, it has not been reported that brucelipid enhances the efficacy of various chemotherapeutic drugs by inhibiting the Nrf2 pathway

Method used

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  • Application of brusatol as chemotherapeutic drug synergist
  • Application of brusatol as chemotherapeutic drug synergist
  • Application of brusatol as chemotherapeutic drug synergist

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1: Determination of Nrf2 protein expression in non-small cell lung cancer A549, cervical cancer Hela, endometrial cancer Ishikawa and Spec-2, and breast cancer MDA-MB-231 cell lines

[0028] Experimental materials: Non-small cell lung cancer A549, cervical cancer Hela, endometrial cancer Ishikawa and Spec-2, breast cancer MDA-MB-231 cell lines were purchased from ATCC in the United States; bruceicol was isolated from Brucea javanica, NMR and MS Determine the structure; Nrf2 and GAPDH antibodies were purchased from Santa Cruz; cisplatin, carboplatin, etoposide, 5-FU and paclitaxel were purchased from Sigma.

[0029] experimental method:

[0030] (1) Cell treatment: Cells were treated with 1×10 6 The density of cells per well was seeded in 6-well plates, and treated with cholepicrol DMSO solution for 4 hours.

[0031] (2) Cell lysis: After the cell treatment is completed, wash the cells twice with ice PBS to remove residual drugs, add SDS cell lysate 100 μl / well...

Embodiment 2

[0034] Example 2: Brucelipidol increases the effect of cisplatin, carboplatin, 5-FU, etoposide and paclitaxel on A549 cells

[0035] Experimental materials: the sources of cell lines, drugs, and culture medium are the same as those in Example 1.

[0036] Instrument: Roche Xcelligence cell real-time detection system.

[0037] Experimental method: Cells were inoculated in Xcelligence special 16-well plate at a density of 8000 per well. After the cells had adhered to the wall for 16-24 hours, they were pretreated with cholepicol for 4 hours, and then chemotherapeutic drugs were added for co-cultivation. The cell growth index was recorded for 30 minutes and recorded for 72 hours.

[0038] Experimental results: The application of bruceicol alone temporarily inhibited the cells. With the prolongation of the treatment time, the cells in the bruceicol treatment group gradually resumed growth, while the cell growth index of the combined drug group was significantly smaller than that o...

Embodiment 3

[0039] Example 3: Brucelipidol can increase the effect of cisplatin and carboplatin on Hela cells

[0040] Experimental material and experimental method are the same as embodiment 2.

[0041] Experimental results: Brucelipidin showed a synergistic effect with chemotherapeutic drugs in Hela cells, see image 3 .

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Abstract

The invention discloses a new application of brusatol serving as a chemotherapeutic drug synergist, which is combined with a chemotherapeutic drug when in use. The chemotherapeutic drug comprises cis-platinum, carboplatin, oxaliplatin, 5-fluorouracil, paclitaxel, adriamycin or adriamycin. The brusatol provided by the invention can be prepared into an oral preparation or a non-oral preparation accepted pharmaceutically. The beneficial effects of the brusatol applied in preparing the chemotherapeutic drug synergist are as follows: (1) the brusatol can be used in an Nrf2 path, and the killing effect of various chemotherapeutic drugs on the cancer cells can be enhanced; (2) the growth inhibition of low-dose cis-platinum on transplantable tumor of a naked mouse can be increased by the brusatol, thus having clinical application prospects; (3) the cis-platinum content in non-small cell lung cancer cell strains can be increased by the combined use of the brusatol and the cis-platinum; and (4)the toxicity is not discovered when the brusatol and the cis-platinum are together used in the cellular level and in the mouse test work concentration.

Description

technical field [0001] The invention relates to the new application of brucein as a chemotherapeutic drug synergist, the new application of combining with the chemotherapy drug to increase the curative effect of chemotherapy, and the new application of improving the sensitivity of tumor cells to the chemotherapeutic drug. Background technique [0002] At present, chemotherapy is the main method for the treatment of malignant tumors, and tumor drug resistance is one of the important reasons for the failure of chemotherapy. Medicinal properties. The mechanism of tumor drug resistance is very complex. Recent studies have shown that the Nrf2 signaling pathway is highly expressed in tumor tissue and tumor cells, and the main function of the Nrf2 signaling pathway is to mediate cell detoxification and self-protection. Therefore, the high expression of Nrf2 mediates the high expression of Nrf2 target genes including cell detoxification enzymes NQO1, HO-1 and GCS, multidrug resista...

Claims

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Application Information

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IPC IPC(8): A61K31/366A61K45/00A61P35/00A61P35/04
Inventor 任冬梅张唐娜王李梅杨爽
Owner SHANDONG UNIV
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