Novel medicine composition for synergistically enhancing capacity of restraining tumor growth

A composition and drug technology, applied in the application field of new pharmaceutical compositions, can solve the problems of inability to obtain therapeutic effects, difficult clinical treatment of liver cancer, and infrequently found cancer synergies, and achieve the effect of significant curative effect.

Inactive Publication Date: 2015-01-07
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Therefore, the use of large doses of CQ to inhibit autophagy and induce tumor cell death directly may be difficult to apply to the clinical treatment of liver cancer
[0007] Due to the above problems, these substances cannot obtain a satisfactory therapeutic effect, therefore, it is necessary to improve the effect of the above substances on tumor cell growth inhibitory activity, and / or Provides a means of reducing the dose of therapy to reduce the duration of administration and / or reduce potential or harmful side effects to the patient
Despite this need, synergies are not often found in the treatment of cancer

Method used

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  • Novel medicine composition for synergistically enhancing capacity of restraining tumor growth
  • Novel medicine composition for synergistically enhancing capacity of restraining tumor growth
  • Novel medicine composition for synergistically enhancing capacity of restraining tumor growth

Examples

Experimental program
Comparison scheme
Effect test

experiment example 1

[0062] Experimental example 1: Effects of chloroquine and tetrandrine alone and in combination on lung cancer cells, liver cancer cells, glioma cells, cervical cancer cells, rectal cancer cells, and mouse glioma cells

[0063] Using 5 μM tetrandrine or 20 μM chloroquine alone to act on various cancer cell lines for 48 hours, the cell survival did not change significantly. However, when the above cancer cells were treated with 5 μM tetrandrine and 20 μM chloroquine, the cell death rate was significantly increased, and most of the cell death rates were above 50%, such as figure 1 . However, for normal liver epithelial cells L02 and breast epithelial cells HBL-100, combined treatment with 5 μM tetrandrine and 20 μM chloroquine did not significantly affect their survival ( figure 2), the above results show that the combined effect of this double drug has less toxic and side effects on normal cells.

experiment example 2

[0064] Experimental example 2: Plate cloning assay to analyze the effects of tetrandrine and chloroquine alone or in combination on tumor cells A549 and Huh7

[0065] The combination of lower concentrations of tetrandrine and chloroquine has anti-tumor effect further confirmed by plate cloning experiments. like image 3 As shown, the combined effect of 5 μM tetrandrine and 20 μM chloroquine can significantly inhibit the growth of tumor cells, and 90% of A549 and Huh7 cells on the cloning plate have lost their viability, while up to 20% of the cells on the plate clones treated alone lost vitality.

experiment example 3

[0066] Experimental Example 3: Effects of Tetrandrine and Chloroquine Combined Action on Cell A549 Transplanted Tumor

[0067] To further explore the anti-tumor effect of tetrandrine and chloroquine in animals, a tumor xenograft model was established in nude mice. The 32 nude mice subcutaneously injected with A549 cells were randomly divided into four groups, respectively as the control group, the tetrandrine single-drug group, the chloroquine single-drug group and its double-drug combination group; Tetrandrine 25 mg / kg and chloroquine 50 mg / kg were used for body weight. The control group was 0.1% sodium carboxymethyl cellulose. The mice were orally administered three times a week and the tumor diameter was measured and the body weight of the nude mice was weighed. The result is as Figure 4 As shown, in the A549 cell xenograft model, the tumor growth curve and tumor body weight indicated that the double drug had a significant effect of inhibiting tumor growth.

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Abstract

The invention relates to a novel medicine composition capable of synergistically enhancing the capacity of restraining tumor growth. The composition contains tetrandrine and chloroquine. Researches prove that the combined medication of the tetrandrine and the chloroquine with a certain concentration can effectively induce the death of tumor cells; a BALB / c nude mouse is vaccinated with a tumor cell of a person, a tumor is formed, a nude mouse heterograft model is established, and the monitoring on the growth curve of the tumor and the weight of the tumor indicates that the combined medication has the obvious effect of restraining the tumor growth. The invention confirms that the antitumor effect of the medicine combination containing the tetrandrine and the chloroquine is much better than that of the single tetrandrine or the single chloroquine, the medicine combination has an obvious synergistic effect, the basis of clinical combined application of the tetrandrine and the chloroquine for resisting the tumor is provided, and the medicine combination is a potential tumor medicine with high efficiency and low toxicity.

Description

technical field [0001] The present invention relates to a combined drug, in particular to the application of a novel pharmaceutical composition capable of synergistically enhancing and inhibiting tumor growth. Background technique [0002] Malignant tumors (also known as cancers) are mainly caused by uncontrolled cell growth and proliferation mechanisms, which infiltrate into normal tissues locally, and even metastasize to other parts through the lymphatic system and circulatory system in the body. It has the following characteristics: insensitive to growth-inhibiting signals, unlimited proliferation without the control of growth signals; ability to resist apoptosis and promote angiogenesis; ability to invade and migrate. At present, common cancers mainly include lung cancer, liver cancer, colon cancer, cervical cancer, glioma and cervical cancer. Among them, lung cancer has the highest morbidity and mortality rate in the world, accounting for about 13% and 18% respectivel...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4748A61P35/00A61K31/4706
CPCA61K31/4706A61K31/4748A61K2300/00
Inventor 李文化刘鑫梅柳锋梅运军万佳丽
Owner WUHAN UNIV
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