Application of polypeptide ABC transporter inhibitor

A technology of transporter and inhibitor, which is applied in the field of tumor treatment, can solve the problems of normal cell toxicity, etc., achieve the effect of inhibiting proliferation, broad application prospects, and increasing concentration

Active Publication Date: 2020-08-14
HUNAN UNIV OF SCI & ENG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In the previous studies on tumor drug resistance, peptides were used as anticancer agents. Although they have certain selectivity to tumor cells, they often have certain toxicity to normal cells at effective tumor suppressor concentrations, thus limiting their use. Clinical application

Method used

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  • Application of polypeptide ABC transporter inhibitor
  • Application of polypeptide ABC transporter inhibitor
  • Application of polypeptide ABC transporter inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1 Prediction and Analysis of Polypeptide HX-12C Secondary Structure

[0047] The secondary structure of the antimicrobial peptide was predicted by the secondary structure prediction service, and the secondary structure of the antimicrobial peptide was analyzed by circular dichroism chromatography. Such as figure 1 As shown, the secondary structure of the predicted polypeptide HX-12C has very typical characteristics of amphipathic molecules, and its hydrophobic and hydrophilic surfaces are regularly distributed on both sides of the polypeptide helix. The results of circular dichroism analysis confirmed the correctness of the prediction. The circular dichroism showed an irregular secondary structure in the aqueous phase (0.01mol / L PB buffer), and formed a typical secondary structure in the membrane phase (30% TFE or 70% TEF). α-helical structure. And acidic environment is more conducive to the formation of helical structure. Further explained the interaction of...

Embodiment 2

[0048] Example 2 Effect of Polypeptide HX-12C on ABCB1 Transporter Highly Expressed Cell Line

[0049] In order to determine the effect of polypeptide HX-12C on ABC transporters, the sensitivity of ABCB1 overexpressing cell KB-C2 to polypeptide HX-12C was determined. The cytotoxicity of polypeptides in different cell lines was measured by the improved MTT colorimetric method, and 5000 cells / well were seeded in 96-well cell culture plates and cultured overnight. Peptides were added at a specified concentration gradient, and after incubation for 68 hours, 20 μL of MTT solution (4 mg / mL) was added to each well, incubated for another 4 hours, the medium was aspirated, and 100 μL of DMSO was added to dissolve the formaldehyde crystals. Absorbance was measured at 570 nm with a UV / Vis spectrophotometer. The result is as figure 2 Shown, polypeptide HX-12A (FFRKVLKLIRKI), HX-12B (FFRKVLKLIRKIF) and HX-12C cytotoxicity test IC on ABCB1 overexpression cancer cells (KB-C2) 50 The valu...

Embodiment 3

[0050] Example 3 Effect of Polypeptide HX-12C on ABCC1 Transporter Highly Expressed Cell Lines

[0051] In order to determine the effect of polypeptide HX-12C on ABC transporters, the sensitivity of ABCC1 overexpressing cell KB-CV60 to polypeptide HX-12C was determined. The cytotoxicity of polypeptides in different cell lines was measured by the improved MTT colorimetric method, and 5000 cells / well were seeded in 96-well cell culture plates and cultured overnight. Peptides were added at a specified concentration gradient, and after incubation for 68 hours, 20 μL of MTT solution (4 mg / mL) was added to each well, incubated for another 4 hours, the medium was aspirated, and 100 μL of DMSO was added to dissolve the formaldehyde crystals. Absorbance was measured at 570 nm with a UV / Vis spectrophotometer. The results are shown in Table 1. The cytotoxicity test IC 50 The values ​​are 24.95 μM, 7.41 μM and 6.38 μM, respectively. IC of the peptide of its parental cell (KB-3-1) 50 T...

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Abstract

The invention discloses an application of a polypeptide ABC transporter inhibitor. Polypeptide HX-12C as shown in SEQ ID NO.1 is combined with an ABC transporter substrate chemotherapeutic drug to beapplied to preparation of an ABC transporter mediated multi-drug resistant tumor drug. The ABC transporter mediated multi-drug resistant tumor drug composition is composed of the polypeptide HX-12C shown in SEQ ID NO.1 and the ABC transporter substrate chemotherapeutic drug. The polypeptide disclosed by the invention can inhibit the function of ABC transporter, and can increase the concentration of chemotherapeutic drugs in drug-resistant tumor cells when being combined with ABC transporter substrate chemotherapeutic drugs, thereby inhibiting the proliferation of the drug-resistant tumor cells. The application of the polypeptide ABC transporter inhibitor and ABC transporter substrate chemotherapeutic drug combination in preparation of the ABC transporter mediated multi-drug resistant tumordrug has a wide prospect.

Description

technical field [0001] The invention belongs to the field of tumor treatment, and in particular relates to the application of a polypeptide ABC transporter inhibitor. Background technique [0002] In cancer treatment, the emergence of multidrug resistance is the most important factor for chemotherapy failure and tumor recurrence. The molecular mechanism of tumor multidrug resistance is complex, and the high expression of ATP-binding cassette transporter superfamily (ABC family) in tumor tissue is the main reason for tumor multidrug resistance. ABCB1, ABCG2, and ABCC1 are the main members of the ABC transporter family, and they are highly expressed in a variety of tumor tissues. Cancer, liver cancer, prostate cancer, etc. are highly expressed, and ABCC1 is highly expressed in lung cancer, liver cancer, intestinal cancer, breast cancer, etc. ABCB1, ABCG2, and ABCC1 can recognize a variety of anti-tumor chemotherapy drugs, use the energy released by ATP hydrolysis to pump the...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/10A61K45/06A61K31/337A61K31/475A61K31/136A61P35/00
CPCA61K38/10A61K45/06A61K31/337A61K31/475A61K31/136A61P35/00A61K2300/00A61K31/365A61K31/506A61K31/704A61K33/243A61K31/277
Inventor 罗小芳覃佐东汪美凤唐冬芳
Owner HUNAN UNIV OF SCI & ENG
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