Use of tarapanib in the preparation of medicines for treating or preventing hepatitis virus-related diseases
A technology for hepatitis B virus and hepatobiliary disease, applied in the field of medicine, can solve the problems of enhanced radiation toxicity effect, lack of specificity, enhanced cytotoxicity of radiotherapy and chemotherapy, etc., to achieve the effect of improving treatment effect
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Embodiment 1
[0058] Example 1 Taraparib induces the expression of HBx and the chromosomal aberration of the liver cells carrying hepatitis B virus.
[0059] experimental method:
[0060] 1. HBx protein expression and construction of HBV genome integrated cell lines.
[0061]HL02-H1 is a human liver cell line that stably expresses the entire HBV genome. HL02-H1 was deposited in China Center for Type Culture Collection (CCTCC, accession number: C201554). The HBx protein expression cell HL-7702 / HBx and its control cell HL-7702 / pLV were constructed by a lentivirus infection system. The specific methods of lentivirus packaging and infection are conventional techniques and will not be repeated here.
[0062] 2. Taraparib induces chromosomal aberrations in HBx protein expressing cells and hepatitis B virus host cells.
[0063] HL-7702, HL02-H1, HL-7702 / pLV and HL-7702 / HBx cells were inoculated into two culture dishes with a diameter of 6 cm, and after overnight culture, each cell was added wit...
Embodiment 2
[0068] Example 2 Low-dose taraparib specifically inhibits the expression of HBx and the proliferation of hepatitis B virus host liver cells
[0069] experimental method:
[0070] The specific inhibitory effect of taraparib on hepatocytes expressing HBx and hepatitis B virus host was further verified by clonogenic experiments.
[0071] HL-7702, HL02-H1, HL-7702 / pLV and HL-7702 / HBx cells were seeded in 10 cm diameter culture dishes respectively, and 800 cells were added to each culture dish. After culturing overnight, add tarapanib or the same volume of DMSO (control group) the next day. The cells were fixed with methanol after continuous treatment with tarapanib for 10 days, stained with Giemsa stain, and the number of clones was counted. All experiments were repeated 3 times.
[0072] Drug management included taraparib alone and in combination with a platinum compound (cisplatin). The concentration of taraparib single drug treatment is 0, 5, 10, 20, 50 nM; the concentratio...
Embodiment 3
[0082] Example 3 The curative effect of taraparib on hepatitis B virus positive liver cancer
[0083] experimental method
[0084] Twenty-seven 6-week-old athymic female nude mice were randomly divided into 9 groups. Each mouse was inoculated with HL02-H1 in the armpit and groin, and the inoculation quantity was 4x10 6 . The tumor volume is about 70-100 mm 3 start injecting the drug. The drug injection regimen was a combination of taraparib and platinum drugs (cisplatin), and a solvent control group (DMSO) and a cisplatin single drug control group were set up. The specific dosages are as follows: the combined dosage of taraparib is 2.5 mg / kg / day, and the dosages of other inhibitors are: BGB-290: 10 mg / kg / day, BGP-15: 10 mg / kg / day, E7449: 4 mg / kg / day, rucapranib: 10 mg / kg / day, cisplatin dosage 3 mg / kg, twice a week. The drug injection time was 12 days, and the tumor body surface volume was measured on days 2, 5, 7, 8, 9, and 12. Tumor volume was calculated according to th...
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