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Application of Akt inhibitor to preparation of medicament for enhancing anti-hepatoma activity of lycorine

An inhibitor and anti-liver cancer technology, applied in the field of Akt 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 Akt inhibitor to preparation of medicament for enhancing anti-hepatoma activity of lycorine
  • Application of Akt inhibitor to preparation of medicament for enhancing anti-hepatoma activity of lycorine
  • Application of Akt inhibitor to preparation of medicament for enhancing anti-hepatoma activity of lycorine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] 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)

[0044] 1. Lycorine inhibits the growth of hepatocellular carcinoma

[0045] Analysis of the effect of lycorine on three typical human hepatocellular carcinoma cell lines by measuring cell viability by MTT assay

[0046] (HepG2, SMMC-7721, HuH-7), and a non-tumorigenic human hepatic cell line (Chang Liver). 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 Middle b). ...

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 of Human Microtubule-Associated Protein 1 Light Chain 3β (Homo sapiens microtubule associated protein 1 light chain 3beta, MAP1LC3B, LC-3B for short) gene: NM_022818.4 (Update Date: 10-JUL-2017).

[0067] This experiment selects random double-stranded RNA as negative control siRNA, and the name of this random double-stranded RNA is siNC, and the nucleotide sequence from the 5' end to the 3' end of a strand of siNC is (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 from the 5' end to the 3' end of a chain of LC-3B-1 For (5'-gcucuucuag...

Embodiment 3

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

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

[0082] The experiment was carried out with reference to the corresponding experimental method in Example 1.

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

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Abstract

The invention discloses application of an Akt inhibitor to preparation of a medicament for enhancing the anti-hepatoma activity of lycorine. The invention provides application of the Akt inhibitor tothe preparation of a product for enhancing the anti-hepatoma activity or anti-hepatoma cell activity of the lycorine. As proved by experiments, a hepatoma apoptosis rate after combined use of the Aktinhibitor and the lycorine is higher than the sum of a hepatoma apoptosis rate after separate use of the Akt inhibitor and a hepatoma apoptosis rate after separate use of the lycorine, the Akt inhibitor cooperates with the lycorine on the anti-hepatoma aspect, and the anti-hepatoma activity of the lycorine is improved through the Akt inhibitor.

Description

technical field [0001] The invention relates to the use of Akt inhibitors, in particular to the application of Akt preparations in the preparation of drugs that enhance the anti-liver cancer 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 remaining below 1 year after diagnosis. HCC is a heterogeneous disease originating from chronic liver diseases such as chronic inflammation and cirrhosis. So far, the 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 advanced stage and lose the chance of surgery. Most patients who have undergone surgery in time will still have recurrence and metastasis. Among chemotherapeutic agents, sorafenib, a small-molecule multikinas...

Claims

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Application Information

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IPC IPC(8): A61K45/06A61K31/5377A61K31/437A61P35/00
CPCA61K31/437A61K31/5377A61K45/06A61K2300/00
Inventor 于海洋邱玉玲王涛张祎高秀梅庞旭韩立峰吴淞
Owner TIANJIN UNIV OF TRADITIONAL CHINESE MEDICINE
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