货号：B0115

储存条件：粉末-20°C可保存3年；液体-80°C可保存12月。

产品描述

The proteasome is a catalytic enzyme complex responsible for the degradation of intracellular proteins. Bortezomib is a dipeptide boronate that potently inhibits proteasome with a Ki value of 0.6 nM. After 48-hour incubation, bortezomib at 0.1 μM completed inhibited the growth of different human multiple myeloma (MM) cell lines, including U266, IM-9 and Hs Sultan cells. In U266 and patient primary MM cells, the treatment of 0.01 μM bortezomib induced a progressive increase of sub-G₀/G₁ phase cells in a time-dependent manner from 0 – 16h. Apoptosis as indicated by DNA fragmentation was also promoted by bortezomib treatment. H460 cells treated by 0.01 – 10 μM bortezomib for 24 hours showed increased cell accumulation at G₂-M phase and cell apoptosis in a dose-dependent manner compared to control cells. Bortezomib treatment also led to concentration-dependent phosphorylation of Bcl-2 proteins. When cells were exposed to higher doses of bortezomib (0.1 – 10 μM) for 24 hours, the superphosphorylated form of Bcl-2 was detected. After the exposure to 0.01 – 0.05 μM bortezomib for 24 hours, or 0.1 μM bortezomib for 12 hours, the first cleavage fragment of Bcl-2 protein was detected. The second cleave fragment of Bcl-2 was only found in cells treated with 0.1 μM bortezomib for 12 hours. After incubating with 0.1 μM bortezomib for 24 hours, the phosphorylated Bcl-2 bands were observed in both Triton-X-100 soluble and insoluble fraction. In vivo study showed that 3 times per week injection of 2 mg/kg bortezomib for 25 days inhibited the growth of murine and human squamous cell carcinoma in mice.

作用机制

Bortezomib inhibits proteasome by reversibly binding to the chymotrypsin-like subunit of the proteasome.

产品性质