Interactions Sorafenib Of And Pyrrolidine Dithiocarbamate In Pancreatic Cancer Cells

Objective: To investigate the multiple molecular targeted agents sorafenibassociatedwith Pyrrolidinedithiocarbamate in human Pancreatic cancer PANC-1cellproliferation，cell cycle and expression of NF-kB， and explore its possiblemechanism.Methods: Logarithmic phase human pancreatic cancer cell line PANC-1cells areused in the experiment. The experiment group is divided into three groups,sorafenibgroup, PDTC group and a group that uses both drugs.Besides. a control group is set inwhich no drug is added. MTT method is used to detect antiproliferative ratio ofsorafenib and Pyrrolidinedithiocarbamate in human Pancreatic cancer PANC-1cell;flow cytometry to analyze human Pancreatic cancer PANC-1Cell cycle;Immunocytochemical detection of human Pancreatic cancer PANC-1cell NF-kBprotein expression.Results:1.MTT results shows that: Sorafenib and Pyrrolidinedithiocarbamate could inhibitproliferation of human Pancreatic cancer PANC-1and appeared time-dose-dependenteffects (P<0.05);48hours after, calculated the result of half effective inhibitionconcentration(IC50),Sorafenib14.102μmol/L, PDTC for105.717μmol/L,Theconcentration values are high, indicate that sorafenib and PDTC could not inhabitPANC-1efficiently, however, when low concentration of sorafenib（3μmol/L）associated withPDTC（25μmol/L）,can significantly improve the inhibition of cellproliferation（P<0.05）.2.Flow cytometry results showed that: compared with the control group, after48hours treatment with sorafenib (3μmol/L), PDTC (25μmol/L), sorafenib (3μmol/L)+PDTC (25μmol/L), PANC-1cells that are in G0/G1phase increased with apercentage of (50.93±3.51,48.07±1.70,74.07±2.40)%, while the control group(37.97±1.21)%; corresponding reduction in the number of S-phase cells, respectively(37.30±1.70,38.17±0.51)%, while the S-phase fraction of the control group (45.33±2.03)%, the difference was statistically significant (P <0.05). Which means sorafenib, PDTC sorafenib+PDTC group cell G0/G1phase arrest occurred (P <0.05),and sorafenib+PDTC group statistically most significant.3.Immunohistochemical assay results showed that in the control group: NF-κBisexpressed in pancreatic cancer PANC-1cells both in the cytoplasm and nucleus,48hours after sorafenib induced,the expression of NF-κBin the nucleus of pancreaticcancer PANC-1is significantly enhanced. However,48hafterinducedof PDTCassociated with sorafenib, the expressionof NF-κB inpancreatic cancer PANC-1cellnuclear decreased significantly.Conclusion: Sorafenib and Pyrrolidinedithiocarbamate can significantly inhibithuman Pancreatic cancer PANC-1cells growth in vitro， but IC50values are high.Compared with usingsorafenib alone, PDTC associated with sorafenib cansignificantly improve the inhibition the proliferation ofhuman Pancreatic cancerPANC-1,force them to stay in the phase of G0/G1. Sorafenib will induct theactivation of NF-κB, while PDTCdoes the opposite. Therefor, PDTC can enhance thesensitivity of PANC-1cells to sorafenib.