Abstract
Objective To investigate the mechanism and effect of matrine on the growth of human breast cancer MCF-7/ADR cell xenograft model in nude mice. Methods A total of 20 nude mice were subcutaneously inoculated with MCF-7/ADR cells. After the successful establishment of xenograft model, the 20 nude mice were randomly divided into 4 groups, 5 rats in each group. Low- and high-dose matrine groups were intraperitoneally injected with matrine at dose of 50 and 100 mg/kg respectively. Positive control group was treated orally with MK2206 at dose of 120 mg/kg, and negative control group received normal saline. At 2st day after treatment, the tumor inhibition rate was measured, the mRNA and protein expression of multidrug resistance (MDR)1, phosphatase and tensin homologue deleted on chromosometen (PTEN), protein kinase B (Akt), B cell lymphoma/leukemia-2 associated X protein (bax), B cell lymphoma/leukemia-2 (bcl-2) and cysteinyl aspartate-specific protease-3 (Caspase-3) was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting respectively. Results The tumor inhibition rate in positive control group, low-dose and high-dose matrine groups was 37.9%, 42.1% and 60.7% respectively. RT-PCR showed the MDR1 gene relative expression in low- and high-dose matrine groups was 0.548±0.054, and 0.869±0.058, and the Caspase-3 gene relative expression was 1.642±0.062 and 1.327±0.068 respectively (P 0.05). Western blotting showed the protein expression levels of PTEN, bax and Caspase-3 in positive control group, low-dose and high-dose matrine groups were significantly increased, and those of permeability glycoprotein (P-gp), p-Akt and bcl-2 were significantly decreased as compared with the negative control group (P<0.05). Conclusion Matrine could inhibit the growth of MCF-7/ADR cell xenograft model in nude mice by affecting Akt key gene and regulating the expression of apoptosis-related genes though PI3K/Akt signal pathway. Key words: Matrine; Breast cancer; Apoptosis; Phosphatidylinositol 3 kinase/protein kinase B signal pathway; Nude mice
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