Application of composition of artemisinin or derivative thereof and EGFR-TKI targeted drug

A technology of EGFR-TKI and derivatives, applied in the field of medical applications, can solve problems such as incomplete clarification, and achieve the effect of enhancing the effect of anti-head and neck tumors

Inactive Publication Date: 2019-03-08
JIANGSU PROVINCE INST OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, T790M mutation and c-MET amplification account for more than 50% of EGFR-TKI acquired drug resistance, and the mechanism of the other half is still not completely clear

Method used

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  • Application of composition of artemisinin or derivative thereof and EGFR-TKI targeted drug
  • Application of composition of artemisinin or derivative thereof and EGFR-TKI targeted drug
  • Application of composition of artemisinin or derivative thereof and EGFR-TKI targeted drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Example 1: Artemisinin derivatives and EGFR-TKI synergistically promote head and neck tumor cell death

[0026] Different concentrations of artemisinin derivatives and EGFR-TKI were applied to head and neck tumor cell line Fadu or CAL27 cells for 72 hours, respectively, and the cell viability was detected by MTT method.

[0027] The results show that the combination of artemisinin derivatives and EGFR-TKI is superior to single administration in inhibiting the growth of head and neck tumor cells ( figure 2 ). According to the formula: survival rate = (A 570nm -A 630nm ) treated / (A 570nm -A 630nm ) control ×100% was used to calculate the survival rate. CalcuSyn software was used to calculate the Combination Index (CI). According to the Chou-Talalay definition, CI1 defined the two drugs as an antagonistic effect. The combined drug index of DHA and Osi on Fadu cells was 0.467, and the combined drug index on CAL27 cells was 0.547, both of which had synergistic effe...

Embodiment 2

[0031]Example 2: Dihydroartemisinin and EGFR-TKI inhibit the colony formation ability of head and neck tumor cells

[0032] Take Fadu and CAL27 cells in the logarithmic growth phase, and use 2×10 3 The cell density of each cell / well was inoculated into a six-well plate, and after 24 hours of culture, the RPMI 1640 medium containing 1% FBS was replaced, and different concentrations of DHA, EGFR-TKI or a combination of the two were added. After 3 days of drug intervention, the RPMI 1640 medium containing 10% FBS was replaced to continue culturing for 10 days. After the experiment, the cells were washed once with PBS, fixed and stained with 0.5% crystal violet (prepared in 10% methanol) for 15 min, and the number of clones formed by 50 cells was recorded.

[0033] The results showed that the combination of dihydroartemisinin and EGFR-TKI was superior to single administration in inhibiting the colony formation of head and neck tumor cells ( image 3 ).

Embodiment 3

[0034] Example 3: Dihydroartemisinin and Osimertinib Inhibit the Growth of Human Head and Neck Tumor Cell Xenografts in Nude Mice

[0035] Take Fadu and CAL27 cells in the logarithmic growth phase, digest with trypsin to make 2x 10 7 cell suspension per ml, inoculate 200 μL (100 μL Matrigel + 100 μL cells) cell suspension into the right armpit of nude mice through a 1 ml syringe, and wait until the tumor grows to 100 mm 3 Dosing in groups when left or right. The groups were as follows: ① solvent control group (0.5% CMC-Na), 5 rats; ② dihydroartemisinin group (50 mg / kg), 5 rats; ③ osimertinib group (5 mg / kg), 5 rats; ④ Dihydroartemisinin and osimertinib combination group, 5 rats. Intragastric administration for one month, body weight and tumor size were measured every three days, according to the formula V=ab 2 Tumor size was calculated by / 2 (a = long diameter, b = short diameter). At the end of the experiment, the nude mice were killed by spinal dislocation, and the tumor...

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Abstract

The invention discloses application of a composition of artemisinin or a derivative thereof and an EGFR-TKI targeted drug in preparation of drugs for treating tumors of the head and neck. Experimentsprove that the artemisinin and the derivative (such as dihydroartemisinin) thereof can reverse drug resistance of the tumors of the head and neck to the targeted drug, and when the artemisinin and thederivative thereof are combined to the target drug to treat the tumors of the head and neck, a remarkable synergistic effect is achieved. Through experiments, it proves that the artemisinin and the derivative such as dihydroartemisinin thereof can inhibit protein phosphorylation such as STAT3, paxillin and FAK, by the activity, the effect of resisting the tumors of the head and neck of the targeted drug (such as osimertinib as an EGFR inhibitor) is enhanced, and pharmacological basis is provided for developing new application of artemisinins drugs.

Description

technical field [0001] The invention belongs to the field of medical applications, and relates to the application of artemisinin and its derivatives in the preparation of drugs for treating head and neck tumors. Background technique [0002] Head and neck cancer includes tumors originating from any tissue or organ in the head and neck except the eyes, brain, ear, thyroid and esophagus, mainly in the sinuses, nasal cavity, oral cavity, tongue, salivary glands, pharynx, larynx, etc. parts. Head and neck tumors are mostly cancerous squamous cells that line the moist mucous surfaces of the head and neck, such as inside the mouth, nose, and throat. These squamous cell carcinomas are often referred to as head and neck squamous cell carcinomas (head and neck squamous cell carcinoma, HNSCC), accounting for about 90% of head and neck tumors. Head and neck tumors can also arise from the salivary glands, but salivary gland cancers are relatively uncommon. Head and neck tumors are on...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/366A61K31/357A61K45/06A61P35/00
CPCA61K31/357A61K31/366A61K45/06A61P35/00A61K2300/00
Inventor 曹鹏拉斐尔罗塞尔蔡雪婷
Owner JIANGSU PROVINCE INST OF TRADITIONAL CHINESE MEDICINE
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