Compound anti-cancer drug combining statin cholesterol-lowering drugs with thiazine antihypertensive drugs

An anti-cancer drug and thiazide technology, which can be used in drug combinations, pharmaceutical formulations, active ingredients of heterocyclic compounds, etc., can solve problems such as toxic side effects of life, endangering patients, and increasing toxic and side effects

Active Publication Date: 2014-01-08
INT HEALTHCARE INNOVATION INST JIANGMEN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When monotherapy is used, although increasing the dose can improve the curative effect, it is followed by an increase in toxic and side effects
And quite a few antineoplastic drugs have toxic and side effects that may endanger the lives of patients

Method used

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  • Compound anti-cancer drug combining statin cholesterol-lowering drugs with thiazine antihypertensive drugs
  • Compound anti-cancer drug combining statin cholesterol-lowering drugs with thiazine antihypertensive drugs
  • Compound anti-cancer drug combining statin cholesterol-lowering drugs with thiazine antihypertensive drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Example 1: The effect of administration of atorvastatin and hydrochlorothiazide on NF-κB of prostate cancer VCaP-N cells

[0022] Prostate cancer VCaP / N cells were inoculated at a density of 0.01×106 cells / ml and cultured for 24 hours. Then treated with atorvastatin and hydrochlorothiazide for 24h. The activity of NF-κB protein was detected by the method of luciferase reporter gene. The luciferase gene was introduced into PC-3 cells to form a stable clone, and then administered alone or in combination for 24 hours; then the luciferase detection kit was used to detect the activity of NF-kB luciferase, which indirectly reflected NF- kB level.

[0023] deal with Luciferase activity (% control group) Control group100 Atorvastatin group (10μM)89.2 Hydrochlorothiazide group (10μM)90.3 Atorvastatin (10μM) + Hydrochlorothiazide (10μM) group66.5

[0024] As can be seen from the table, the luciferase activity (% of the control group) of the atorvastatin (10μM) and hydr...

Embodiment 2

[0025] Example 2: The effect of administration of atorvastatin and hydrochlorothiazide on prostate cancer PC-3 cells

[0026] PC-3 cells were seeded in a 35mm petri dish at a density of 0.02x106 cells / ml and cultured for 24h. Then treated with 10 μM atorvastatin and hydrochlorothiazide for 96h. The number of live and dead cells was measured by trypan blue exclusion test. After an appropriate incubation time, collect the cells, stain them with trypan blue, count the blue-stained and non-stained cells under an inverted microscope, and use the formula "live cell rate (%) = total live cells / (total live cells + total dead cells) ×100%" to calculate cell survival rate.

[0027] deal with Number of living cells (1x104) Cell death rate (%) Growth inhibition rate (%) Control group37.22.9- Hydrochlorothiazide group (10μM)32.87.511.8 Atorvastatin group (10μM)35.34.05.1 Hydrochlorothiazide (10μM) + Atorvastatin (10μM) group 24.322.634.7

[0028] It can be seen from the table th...

Embodiment 3

[0029] Example 3: Effect of administration of atorvastatin and hydrochlorothiazide on prostate cancer CWR cells

[0030] CWR cells were seeded in 35mm petri dishes at a density of 0.02x106 cells / ml and cultured for 24h. Then treated with hydrochlorothiazide and atorvastatin at a concentration of 10 μM for 96 h. The number of live and dead cells was measured by trypan blue exclusion test. After an appropriate incubation time, collect the cells, stain them with trypan blue, count the blue-stained and non-stained cells under an inverted microscope, and use the formula "live cell rate (%) = total live cells / (total live cells + total dead cells) ×100%" to calculate cell survival rate.

[0031] The effects are as follows:

[0032]

[0033] It can be seen from the table that the PC-3 cell growth inhibition rate (% of the control group) in the atorvastatin (10μM) and hydrochlorothiazide (10μM) groups alone was 33.1% and 28.1%, while the combined administration group (A The torvast...

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PUM

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Abstract

The invention provides a compound anti-cancer drug comprising statin drugs and thiazine drugs. Statin drugs are safe and effective hypercholesteremia-controlling drugs widely used in clinic, and can inhibit 3-hydroxy-3-methyl coenzyme A (HMG-CoA) reductase. Hydrochlorothiazide is a thiazine diuretic and antihypertensive drug. The invention shows that low-dose combined administration of atorvastatin and hydrochlorothiazide can more effectively inhibit growth of prostate cancer cells, pancreatic cancer cells, and colon cancer cells than single high-dose administration.

Description

Technical field [0001] The invention relates to a combined anti-cancer drug, and more specifically, to a compound anti-cancer drug that combines a statin cholesterol lowering drug and a thiazide antihypertensive drug. Background technique [0002] Cancer is a malignant disease that seriously threatens human health and one of the main "killers" of human death. In the past 30 years, cancer mortality in China has increased by 80%, accounting for a quarter of the global cancer deaths, and the incidence is becoming younger. In 2010, the World Health Organization No. 2 warned that if people do not take serious measures to prevent cancer, by 2030, the annual number of cancer deaths worldwide will likely double to 17 million on the existing basis. [0003] Prostate cancer is a malignant tumor that occurs in male prostate tissue. The incidence increases with age, and its incidence has obvious geographic and ethnic differences. In developed countries and regions such as Europe and the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/549A61P35/00A61K31/40
Inventor 郑希杜志云张焜苏博云王华倩艾伦·康尼卢宇靖赵肃清郑杰黄华容谭伟周丽华陈迁刘艳郑俊霞丁金龙
Owner INT HEALTHCARE INNOVATION INST JIANGMEN
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