刘国忠, 石铮, 郭回希. Interactions sorafenib of and pyrrolidine dithiocarbamate in pancreatic cancer cells[J]. China Oncology, 2013, 23(6): 425-431. DOI: 10.3969/j.issn.1007-3969.2013.06.005.
Interactions sorafenib of and pyrrolidine dithiocarbamate in pancreatic cancer cells
can inhibit proliferation and induce apoptosis of diverse tumor cell in vitro. It has extensive biological activities
but the pancreatic cancer effect of monotherapy is poor. This may be related to nuclear factor-kappa
B (NF-κB) pathway activation in cancer. Therefore
it is necessary to combine with Pyrrolidinedithiocarbamate (PDTC
a NF-κB activation inhibitor) to enhance curative effect. To investigate the influences of cell proliferation
cell cycle and expression of NF-κB via their acting on human pancreatic cancer PANC-1
and explore their possible mechanism. Methods: The experiment groups were divided into sorafenib group with different concentrations (1.5
3.0
6.0
12.0 μmol/L)
PDTC group with different concentrations (10.0
25.0
50.0
100.0 μmol/L) and combination group with low concentration (3.0 μmol/L sorafenib +25.0 μmol/L PDTC). The proliferative activity of PANC-1 of each group was measured by MTT assay at different time points of 24
36
48 and 72 h
and the half inhibitory concentration (IC
50
) was calculated
respectively. Cell cycle in each group was detected by flow cytometry instrument after 48 h. The changes of NF-κB expression level in each group were observed by immunocytochemistry after 24 h. Results: Sorafenib and PDTC can significantly inhibit the proliferation of PANC-1
but IC
50
value of the single medicine was higher
combination group with low concentration can significantly increase the cell growth inhibition rate (P0.05). Three groups can induce the cell stagnation at G
0
/G
1
phase (P0.05) and cells at S phase were decreased. The effect of combination group with low concentration was better than the single drug group (P0.05). The NF-κB expression level in sorafenib group was significantly enhanced
while the level in combination group was significantly decreased (P0.05). Conclusion: Sorafenib and PDTC can significantly inhibit the growth of human pancreatic cancer PANC-1 cells in vitro
but the effect of one drug is unsatisfactory. PDTC combined with sorafenib significantly improve the inhibition rate of the proliferation of human pancreatic cancer PANC-1
and induce the cell stagnation at G
0
/G
1
phase. This may relate to inhibit
the activation of NF-κB by PDTC and enhance the sensitivity of PANC-1 cells to sorafenib.