Application of combination of zoledronic acid and organic selenium compound in preparation of antitumor drugs

An anti-tumor drug, zoledronic acid technology, applied in the field of tumor treatment, can solve the problems of tumor cell apoptosis, DNA damage, cell cycle arrest, etc., and achieve the effect of efficiently inducing tumor cell apoptosis

Active Publication Date: 2019-06-21
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] The results of the study showed that selenodiazole derivatives can inhibit the activity of TrxR in tumor cells, affect the clearance of ROS, and cause them to accumulate rapidly in tumor cells, resulting in DNA damage, cell cycle arrest, and finally induction of tumor cell apoptosis.

Method used

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  • Application of combination of zoledronic acid and organic selenium compound in preparation of antitumor drugs
  • Application of combination of zoledronic acid and organic selenium compound in preparation of antitumor drugs
  • Application of combination of zoledronic acid and organic selenium compound in preparation of antitumor drugs

Examples

Experimental program
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Effect test

Embodiment 1

[0036] Example 1 Study on anti-prostate tumor activity in vitro of ZOL and organic selenium compounds

[0037] In this experiment, we studied the in vitro antitumor activity of organic selenium compounds and ZOL on prostate cancer PC-3 cells. We look forward to the development of novel synergistic chemotherapy strategies for the treatment of tumors.

[0038] (1) Prostate cancer cells in logarithmic growth phase (PC-3 cells; purchased from American Type Culture Collection) were taken at a density of 2×10 4 cells / mL were seeded in 96-well plates (100 μL / well) and allowed to grow for 2 hours. PC-3 cells were pretreated with 20 μM ZOL for 8 h, and then 2 μM organic selenium compounds SeC and SeD (100 μL) were added to a 96-well plate, and no addition of ZOL and organic selenium compounds was used as a blank control, and the incubation was continued for 64 hours. After the time was up, 25 μL of MTT solution (5 mg / mL, PBS buffer) was added to each well and incubated for 4 hours. ...

Embodiment 2

[0055] Example 2 Study on the Effects of ZOL and Organoselenium Compounds on ROS Levels of Prostate Tumors

[0056] The excessive accumulation of reactive oxygen species ROS in cells is an important initial signal to cause cell damage, so we detected the effect of ZOL combined with organic selenium compounds (SeC, SeD) on prostate cancer cells after staining with DHE probes. Impact. The specific method is as follows:

[0057] The cells were inoculated in a 96-well plate at a density of 200,000 cells / mL. After the cells adhered to the wall for 24 hours (the medium used for culturing cells was DMEM medium), 50 μL of 20 μM ZOL was added to incubate for 2 to 8 hours as required. Afterwards, the DMEM medium was replaced with 20 μM, 100 μL DHE probe per well, incubated in the dark for 30 min, and SeC and SeD were added after ZOL incubation according to the requirements of each group (the concentration of SeC and SeD can be 0.25-8 μM; this paper The concentration of SeC and SeD use...

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Abstract

The invention discloses application of the combination of zoledronic acid and an organic selenium compound in preparation of antitumor drugs. In-vitro cell experiments show that the inhibiting effectof the organic selenium compound alone or the zoledronic acid alone on tumor cells is not as good as that of the combination of the two, and the combination of the two can achieve a synergistic effect, that is, the synergistic effect of the organic selenium compound and the zoledronic acid can be utilized to efficiently induce apoptosis of the tumor cells. According to the application, the potential mechanism of action, in which the ability of the organic selenium compound to inhibit the growth of prostate cancer cells is enhanced by the zoledronic acid, is caused by the fact that the cells are induced to generate excessive ROS (reactive oxygen species). The zoledronic acid and the organic selenium compound can be combined to prepare the antitumor drugs, or the zoledronic acid is used as asensitizer for the organic selenium compound and is applied to the field of tumor therapy.

Description

technical field [0001] The invention relates to the technical field of tumor treatment, in particular to the combined use of zoledronic acid and an organic selenium compound in the preparation of antitumor drugs. Background technique [0002] Prostate cancer is one of the common malignant tumors of the male genitourinary system, and the incidence rate is increasing year by year and tends to be younger. Because the onset of prostate cancer is hidden, its symptoms are often ignored. When it is diagnosed, about 65% to 75% have already There is bone metastases. Prostate cancer bone metastasis will cause a series of bone-related diseases, including pathological fractures, spinal cord compression, malignant tumor hypercalcemia, etc. Bone pain is the most common symptom of advanced prostate cancer, which seriously affects the quality of life of patients. Therefore, how to improve the treatment effect while relieving the patient's pain and ensuring the quality of life of the patien...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/675A61K31/198A61K31/4184A61P35/00A61P13/08
Inventor 赵建夫陈填烽贺利贞段琳琪安玉琳
Owner JINAN UNIVERSITY
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