Application of the Chinese medicine monomer isodeoxycholic acid in the preparation of anticancer drugs

Abstract

The present invention discloses an application of a Chinese medicine monomer isodeoxycholic acid in the preparation of an anticancer drug, wherein the anticancer drug is used to treat liver cancer; the active ingredient of the anticancer drug comprises the Chinese medicine monomer isodeoxycholic acid. Experimental results show that the Chinese medicine monomer isodeoxycholic acid can well inhibit the proliferation of liver cancer cells, and at the same time, combined with sorafenib can achieve a synergistic effect, which provides a new strategy for the clinical treatment of liver cancer, and also provides a new idea for the further development of the Chinese medicine monomer isodeoxycholic acid.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine, and specifically relates to the application of a traditional Chinese medicine monomer, isodeoxycholic acid, in the preparation of anticancer drugs. Background Art

[0002] Liver cancer (HCC) is a malignant tumor of the liver, which can be divided into two categories: primary and secondary. Primary liver malignant tumors originate from the epithelial or mesenchymal tissue of the liver. They are highly prevalent and extremely harmful malignant tumors. Liver cancer is one of the common malignant tumors in my country, and its mortality rate ranks third among malignant tumors, second only to gastric cancer and esophageal cancer. It is of great significance to develop new drugs and strategies for the treatment of liver cancer.

[0003] Isodeoxyelephantopin is a bioactive ingredient extracted from the traditional Chinese medicine Eleutherococcus elegans, which has multiple pharmacological effects such as anti-inflammatory, anti-tumor and liver protection. Previous studies have shown that isodeoxyelephantopin can inhibit the growth of various tumor cells, but its inhibitory activity against liver cancer cells in combination with other drugs has not been reported. Summary of the invention

[0004] The present invention provides an application of a Chinese medicine monomer isodeoxycholic acid in the preparation of an anticancer drug, which provides a new strategy for the clinical treatment of liver cancer and has a good effect.

[0005] The technical solution of the present invention is as follows:

[0006] Use of a Chinese medicine monomer, isodeoxycholic acid, in the preparation of an anticancer drug, wherein the anticancer drug is used to treat liver cancer;

[0007] The active ingredients of the anticancer drug consist of traditional Chinese medicine monomers isodeoxycholic acid and sorafenib.

[0008] The experimental results showed that isodeoxycholic acid can significantly inhibit the growth of colon cancer cells (HCT15 and HCT116), liver cancer cells (Huh7 and HepG2) and lung cancer cells (H460 and A549). Interestingly, compared with other tumor cells, it has the strongest inhibitory activity on liver cancer cells. Further studies have shown that isodeoxycholic acid can inhibit the proliferation of liver cancer cells Huh7 and HepG2 in a concentration-dependent manner, and has little effect on the proliferation of normal liver cells MIHA, indicating that it can selectively kill tumor cells and has great development potential.

[0009] At the same time, the experimental results showed that compared with single drugs, isodeoxycholic acid combined with conventional chemotherapy drug 5-fluorouracil had no significant synergistic effect. At the same concentration, it had stronger anti-liver cancer activity when combined with sorafenib. The corresponding combination index showed that the combined treatment of cells with the two had a synergistic anti-tumor effect (CI value less than 1), and showed strong synergistic effect (CI value less than 0.5) when the final concentration was 5μM.

[0010] Preferably, the molar ratio of the Chinese medicine monomer isodeoxycholic acid to sorafenib is 2.5-5:2.5-5. Further preferably, the concentration of the Chinese medicine monomer isodeoxycholic acid is 2.5-5 μM, and the concentration of sorafenib is 2.5-5 μM; most preferably, the concentration of the Chinese medicine monomer isodeoxycholic acid is 5 μM, and the concentration of sorafenib is 5 μM. At this time, the Chinese medicine monomer isodeoxycholic acid and sorafenib can play a better synergistic role in the treatment of liver cancer.

[0011] The present invention also provides a pharmaceutical composition, which consists of the traditional Chinese medicine monomers isodeoxycholic acid and sorafenib.

[0012] Preferably, the molar ratio of the Chinese medicine monomer isodeoxycholic acid to sorafenib is 2.5-5:2.5-5. Most preferably, the concentration of the Chinese medicine monomer isodeoxycholic acid is 5 μM, and the concentration of sorafenib is 5 μM.

[0013] The present invention provides the above-mentioned new combined drug regimen, which provides a new strategy for the clinical treatment of liver cancer, and also provides a new idea for the further development of the traditional Chinese medicine monomer isodeoxycholic acid. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] Figure 1 The results of the inhibition test of isodeoxycholic acid on the proliferation of different cells in Example 1;

[0015] Figure 2 This is the experimental result of inhibiting liver cancer cell proliferation by isodeoxycholic acid combined with 5-fluorouracil or sorafenib in Example 2. DETAILED DESCRIPTION

[0016] General experimental steps for cell viability:

[0017] The cell survival rate was determined by trypan blue exclusion test. The specific operation steps are as follows: cells (about 200,000) were inoculated into 6-well plates, cultured overnight, and replaced with fresh culture medium with a volume of 1 mL after the cells were completely attached to the wall. The drug was then added for 24 hours. After the drug was applied, the culture medium was removed, the cells were digested, and the number of viable cells was detected by trypan blue staining. The cells in the group with equal amount of DMSO were used as a comparison, and their survival rate was set as 100%, so as to obtain the cell survival rate of different drug treatment groups. The corresponding synergy index was calculated using CompuSyn software. CI>1 indicates antagonism, CI=1 indicates additive effect, and CI<1 indicates synergistic effect.

[0018] Example 1 Inhibition test of isodeoxycholic acid on proliferation of different cells

[0019] Referring to the above experimental process, the inhibitory effect of isodeoxycholic acid on colon cancer cells HCT15 and HCT116, liver cancer cells Huh7 and HepG2, lung cancer cells H460 and A549, and normal liver cells MIHA was tested. The results are shown in Figure 1 .

[0020] in Figure 1 A is the survival rate of colon cancer cells HCT15 and HCT116 after 24 hours of treatment with isodeoxycholic acid (final concentration of 10 μM); Figure 1 B is the survival rate of liver cancer cells Huh7 and HepG2 after 24h of treatment with isodeoxycholic acid (final concentration of 10μM); Figure 1 C is the survival rate of lung cancer cells H460 and A549 after 24h of action of isodeoxycholic acid (final concentration of 10μM); Figure 1 D and Figure 1 F is the survival rate of liver cancer cells Huh7 and HepG2 and normal liver cells MIHA after being treated with different concentrations of isodeoxycholic acid for 24 hours.

[0021] The above results show that isodeoxycholic acid can significantly inhibit the growth of colon cancer cells (HCT15 and HCT116), liver cancer cells (Huh7 and HepG2) and lung cancer cells (H460 and A549). Interestingly, compared with other tumor cells, it has the strongest inhibitory activity on liver cancer cells. Further studies have shown that isodeoxycholic acid can inhibit the proliferation of liver cancer cells Huh7 and HepG2 in a concentration-dependent manner, and has little effect on the proliferation of normal liver cells MIHA, indicating that it can selectively kill tumor cells and has great development potential.

[0022] Example 2 Experiment on the inhibition of liver cancer cell proliferation by isodeoxycholic acid combined with 5-fluorouracil or sorafenib

[0023] Referring to the above experimental method, this example further tested the inhibitory effect of isodeoxycholic acid combined with 5-fluorouracil or sorafenib on liver cancer cells. The results are shown in Figure 2 , Figure 2 In the figure, A is the survival rate of liver cancer cell Huh7 after different concentrations of isodeoxycholic acid and 5-fluorouracil act together for 24 hours; B is the corresponding combination index calculated by CompuSyn software based on the data of Figure A; C is the survival rate of liver cancer cell Huh7 after different concentrations of isodeoxycholic acid and sorafenib act together for 24 hours; D is the corresponding combination index calculated by CompuSyn software based on the data of Figure C; E is the survival rate of liver cancer cell HepG2 after different concentrations of isodeoxycholic acid and sorafenib act together for 24 hours; F is the corresponding combination index calculated by CompuSyn software based on the data of Figure E.

[0024] The above results show that compared with single drugs, isodeoxycholic acid combined with 5-fluorouracil has no significant synergistic effect. At the same concentration, isodeoxycholic acid combined with sorafenib has stronger anti-liver cancer activity. The corresponding combination index shows that the combined treatment of cells has a synergistic anti-tumor effect (CI value is less than 1), and exhibits a strong synergistic effect (CI value is less than 0.5) when the final concentration is 5μM. This result also further shows that the synergistic effect between drugs is selective.

Claims

1. A use of a Chinese medicine monomer isodeoxycholic acid in the preparation of an anticancer drug, characterized in that: The anticancer drug is used to treat liver cancer; The active ingredients are composed of traditional Chinese medicine monomers isodeoxycholic acid and sorafenib.

2. The use of the Chinese medicine monomer isodeoxycholic acid in the preparation of anticancer drugs according to claim 1, characterized in that: The molar ratio of the traditional Chinese medicine monomer isodeoxycholic acid to sorafenib is 2.5-5:2.5-5.

3. The use of the Chinese medicine monomer isodeoxycholic acid in the preparation of anticancer drugs according to claim 2, characterized in that: The concentration of the Chinese medicine monomer isodeoxycholic acid is 2.5-5 μM, and the concentration of sorafenib is 2.5-5 μM.

4. The use of the Chinese medicine monomer isodeoxycholic acid in the preparation of anticancer drugs according to claim 1, characterized in that: The concentration of the Chinese medicine monomer isodeoxycholic acid is 5 μM, and the concentration of sorafenib is 5 μM.

5. The use of the Chinese medicine monomer isodeoxycholic acid in the preparation of anticancer drugs according to any one of claims 1 to 4, characterized in that: The anticancer drug is used for inhibiting liver cancer cells Huh7 and HepG2.

6. A pharmaceutical composition, characterized in that It is composed of the traditional Chinese medicine monomers isodeoxycholic acid and sorafenib.

7. The pharmaceutical composition according to claim 6, characterized in that The molar ratio of the traditional Chinese medicine monomers isodeoxycholic acid and sorafenib is 2.5-5:2.5-5.

8. The pharmaceutical composition according to claim 6, characterized in that The concentration of the Chinese medicine monomer isodeoxycholic acid is 5 μM, and the concentration of sorafenib is 5 μM.

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