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Application of autophagy inhibitor to preparation of medicament for reinforcing anti-hepatoma activity of lycorine

An autophagy inhibitor and anti-liver cancer technology, applied in the field of autophagy inhibitors, can solve problems such as unclear molecular mechanism

Active Publication Date: 2019-02-05
TIANJIN UNIV OF TRADITIONAL CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, its precise molecular mechanism is still unclear

Method used

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  • Application of autophagy inhibitor to preparation of medicament for reinforcing anti-hepatoma activity of lycorine
  • Application of autophagy inhibitor to preparation of medicament for reinforcing anti-hepatoma activity of lycorine
  • Application of autophagy inhibitor to preparation of medicament for reinforcing anti-hepatoma activity of lycorine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1. Autophagy inhibitors enhance the anti-liver cancer activity of lycorine (the combination of autophagy inhibitors and lycorine enhances the apoptosis of liver cancer cells)

[0045] 1. Lycorine inhibits the growth of hepatocellular carcinoma

[0046] The cell viability was determined by MTT assay, and the growth inhibitory effect of lycorine on three typical human hepatocellular carcinoma cell lines (HepG2, SMMC-7721, HuH-7) and the non-tumorigenic human liver cell line (ChangLiver ). HepG2, SMMC-7721, HuH-7 and Chang Liver were cultured for 48 hours with the medium containing lycorine at 0, 10, 20, 30, 40 and 50 μM respectively, and the cell viability was determined by MTT method. The results showed that 10, 20 , 30, 40, and 50 μM lycorine were treated for 48 hours, and the viability of liver cancer cells was significantly reduced. At the same time, lycorine did not affect the cell viability of normal liver cells Chang Liver at the same dose ( figure 1 Midd...

Embodiment 2

[0065] Example 2. siRNA targeting LC-3B enhances the anti-liver cancer activity of lycorine, and siRNA targeting LC-3B and lycorine have a synergistic effect in anti-liver cancer

[0066] NCBI Reference Sequence: NM_022818.4 (Update Date: 10-JUL-2017) of the human microtubule associated protein 1 light chain 3beta (Homo sapiens microtubule associated protein1 light chain 3beta, MAP1LC3B, LC-3B for short) gene.

[0067] In this experiment, random double-stranded RNA was selected as the negative control siRNA. The name of the random double-stranded RNA was siNC. The nucleotide sequence from the 5' end to the 3' end of one chain of siNC was (5'-uucuccgaacgugucacguTT-3') The nucleotide sequence from the 3' end to the 5' end of the other chain of siNC is (3'-TTaagaggcuugcacagugca-5').

[0068] In this experiment, two siRNAs targeting human LC-3B were selected, named LC-3B-1 and LC-3B-2, respectively. The nucleotide sequence of one strand of LC-3B-1 from the 5' end to the 3' end is...

Embodiment 3

[0080] Example 3. Akt inhibitor enhances the anti-hepatoma activity of lycorine (Akt inhibitor and lycorine in combination enhance the apoptosis of liver cancer cells)

[0081] 1. Lycorine promotes apoptosis and autophagy of liver cancer cells through TCRP1 / Akt / mTOR signaling pathway

[0082] Experiments were carried out with reference to the corresponding experimental methods in Example 1.

[0083] Tongue cancer resistance-associated protein 1 (TCRP1) has been reported to promote tumorigenesis in radiation-resistant oral squamous cell carcinoma by selectively activating PI3K / Akt and NF-KB pathways. like Figure 4 As shown in a, lycorine treatment significantly reduced the expression of TCRP1 protein level in hepatoma cells. However, lycorine treatment did not significantly alter TCRP1 mRNA levels ( Figure 4 In b), this indicates that the TCRP1 protein is largely transferred through proteasomal degradation. Subsequently, treatment with MG-132, a proteasome inhibitor, sign...

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Abstract

The invention discloses application of an autophagy inhibitor to preparation of a medicament for reinforcing the anti-hepatoma activity of lycorine. Experiments prove that the lycorine promotes autophagy of hepatocellular carcinoma; a hepatoma cell apoptosis rate in a case of combination of the autophagy inhibitor and the lycorine is higher than the sum of a hepatoma cell apoptosis rate in a caseof independent application of the autophagy inhibitor and a hepatoma cell apoptosis rate in a case of independent application of the lycorine; the autophagy inhibitor and the lycorine generate a synergistic effect in the aspect of resisting to hepatoma; the autophagy inhibitor reinforces the anti-hepatoma activity of the lycorine. The autophagy inhibitor can take an important effect in the treatment on hepatoma.

Description

technical field [0001] The invention relates to the use of an autophagy inhibitor, in particular to the application of the autophagy inhibitor in the preparation of a drug for enhancing the anti-hepatocellular carcinoma activity of lycorine. Background technique [0002] Hepatocellular carcinoma (HCC) is one of the most common aggressive tumors worldwide. Liver cancer is a highly lethal tumor with median survival rates remaining below 1 year after diagnosis. Liver cancer is a heterogeneous disease arising from chronic liver diseases such as chronic inflammation and cirrhosis. To date, treatment strategies for liver cancer mainly include resection, transplantation, local ablation, and chemotherapy. Because the early symptoms of liver cancer are not obvious, most patients with liver cancer are diagnosed at an advanced stage and lose the opportunity for surgery. Most patients who receive surgery in time will still experience recurrence and metastasis. Among chemotherapeutic ...

Claims

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Application Information

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IPC IPC(8): A61K31/52A61K31/4745A61P35/00
CPCA23L33/10A23L33/105A23V2002/00A61K31/4745A61K31/52A61K2300/00A23V2200/308A23V2250/21
Inventor 于海洋邱玉玲王涛张祎高秀梅韩立峰庞旭刘二伟
Owner TIANJIN UNIV OF TRADITIONAL CHINESE MEDICINE
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