Multi-medicine medicine-resistant RNA interference medicine for resisting tumor

A technology of RNA interference and multi-drug resistance, applied in the direction of anti-tumor drugs, DNA/RNA fragments, drug combinations, etc., can solve problems such as adverse reactions, high toxicity, and limited clinical application

Inactive Publication Date: 2004-02-25
INST OF HEMATOLOGY & BLOOD HOSPITAL CHINESE ACAD OF MEDICAL SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At present, dozens of drugs that can reverse MDR have been reported, but the toxicity of the effectiv

Method used

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  • Multi-medicine medicine-resistant RNA interference medicine for resisting tumor
  • Multi-medicine medicine-resistant RNA interference medicine for resisting tumor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] After K562 / A02 cells were treated with siRNA for 24 hours, the expression of mRNA in the si-mdr1 group was down-regulated by (17.23±2.47)% (p>0.05) compared with the negative control group, and mdr- 1 mRNA expression was significantly reduced, respectively (38±1.23)% and (58±1.54)% (pfigure 1 .

Embodiment 2

[0048] Example 2. P-gp expression detection

[0049] After 48 hours of siRNA action, flow cytometry showed that the three groups inhibited the expression of p170 to varying degrees, and the positive rate of p170 expression in the si-mdr1 action group decreased from (76.0±1.03)% before treatment to (56.72±1.03)% after treatment. 1.41)%, the si-mdr2 effect group decreased to (42.70±1.17)% (p0.05), see figure 2 .

[0050] Changes in drug sensitivity of K562 / A02 cells after RNAi treatment: IC 50 Refers to the concentration of chemotherapeutic drugs when the cell inhibition rate is 50%. It can be seen from Table 1 that after the action of si-mdr2 and si-mdr3, the sensitivity of K562 / A02 to the chemotherapeutic drug ADM increases, suggesting that RNAi can restore the sensitivity of K562 / A02 to chemotherapeutic drugs. sensitivity. Example 3. Reversal effect of siRNA on drug resistance of K562 / A02 cells

Embodiment 3

[0050] Changes in drug sensitivity of K562 / A02 cells after RNAi treatment: IC 50 Refers to the concentration of chemotherapeutic drugs when the cell inhibition rate is 50%. It can be seen from Table 1 that after the action of si-mdr2 and si-mdr3, the sensitivity of K562 / A02 to the chemotherapeutic drug ADM increases, suggesting that RNAi can restore the sensitivity of K562 / A02 to chemotherapeutic drugs. sensitivity. Example 3. Reversal effect of siRNA on drug resistance of K562 / A02 cells

[0051] Table 1 compares the results of siRNA reversal of drug resistance in K562 / A02 cells. Each experiment was repeated 3 times, with 3 parallel wells each time, and the average value was taken. si-mdr1, si-mdr2 and si-mdr3 all have multidrug resistance reversing effects, and si-mdr3 has the most significant effect.

[0052] Table 1

[0053] IC 50 (μg / ml) relative reversal efficiency

[0054] (%)

[0055] K562 0.05 /

[...

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Abstract

The present invention discloses an antitumor multi-drug drug-resistant RNA interference drug, provides a group of nucleotide sequences of interference RNA of therapeutic drug pointed at drug-resistant gene mdr-1 and P-glycoprotein (P-gp) expression and function for resisting leucosis and other tumor. It has the target antitumor cell multidrug drug-resistant (mdr-1) gene and P-glycoprotein (P-gp) expression and function. It raises the sensitivity of leucosis cell conventional chemical therapeutic drug and enhances the action of chemical therapeutic drug for killing malignant tumor cell of hemopoietic system.

Description

technical field [0001] The invention relates to anti-tumor drugs, especially anti-tumor multidrug-resistant RNA interference drugs. Background technique [0002] Multidrug resistance (MDR) is an important obstacle to long-term remission of leukemia and other malignant tumors with conventional chemotherapy. Studies have shown that the overexpression of p-glycoprotein (p-glycoprotein, P-gp) encoded by the mdr-1 gene on the surface of tumor cells is the main mechanism leading to multidrug resistance of tumor cells, and it is also a good target for reversing drug resistance. At present, dozens of drugs that can reverse MDR have been reported, but the toxicity of the effective drug concentration is high, causing serious adverse reactions, which limits its clinical application. Therefore, targeted therapy targeting the mdr-1 gene and its protein is a hot spot in research on the reversal of leukemia multidrug resistance at home and abroad. [0003] RNA interference (RNA interfere...

Claims

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Application Information

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IPC IPC(8): A61P35/00C12N15/113
CPCC12N2310/14C12N15/1138C12N2320/31A61P35/00
Inventor 韩忠朝彭智
Owner INST OF HEMATOLOGY & BLOOD HOSPITAL CHINESE ACAD OF MEDICAL SCI
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