Ulinastatin And Taxotere Inhibiting Proliferation And Invasion Of Human Breast Cancer ,and Effect On Expression Of Urokinase Plasminogen Activator ,urokinase Plasminogen Activator Receptor,extracellular Signal-regulated Kinase In Breast Cancer Cell

PART 1 ULINASTATIN AND TAXOTERR INHIBITING PROLIFERATION AND INVASION OF BREAST CANCER CELL MDA-MB-231, AND EFFECT ON EXPRESSION OF UROKINASE PLASMINOGEN ACTIVATOR ,UROKINASE PLASMINOGEN ACTIVATOR RECEPTOR,EXTRACELLULAR SIGNAL-REGULATED KINASEObjective: To observe the effect of ulinastatin (UTI) and Taxotere(TXT) on proliferation and invasion of breast cancer cell line MDA-MB-231(ER-), and expression of urokinase plasminogen activator(uPA), urokinase plasminogen activator receptor(uPAR) , Extracellular signal-regulated kinase(ERK) in vitro.Methods: The breast cancer cell line MDA-MB-231 were treated in randomly divided 4 groups respectively:Control, ulinastatin (UTI,800u/ml) , (TXT,3.7μg/ml), ulinastatin + Taxotere (UTI 800u/ml, TXT 3.7μg/ml). The proliferation of MDA-MB-231 cells are examined by MTT assay ,the invasion ability of cells are tested by Transwell chamber with Matrigel,the expression of mRNA of uPA ,uPAR and ERK are analyzed by real time quantitative reverse transcription-polymerase chain reaction (RQT-PCR) analysis respectively,and Western Blot analysis are launched to quantify the proteins of uPA,uPAR and phosphorylated ERK( p- ERK).Results: In the groups Control, UTI, TXT and UTI+TXT, the proliferation and invasion ability of MDA-MB-231 cells are lower and lower. Gene and protein expression are both down regulated by UTI, and up regulated by TXT; UTI and TXT both have little effect on ERKmRNA, but activation of ERK could be inhibited by UTI and promoted by TXT.Conclusions: UIT could inhibit expression of uPA, uPAR and p-ERK, and it may play a role in enhanced anti-proliferative and anti-invasive effect of TXT on MDA-MB-231 cell. PART 2 ULINASTATIN AND TAXOTERR INHIBITING TUMOR GROWTH,AND EFFECT ON EXPREESSION OF UPA, UPAR, P-ERK OF TRANSPLANTABLE TUMOR OF MDA-MB-231 CELL IN NUDE MICEObjective: To investigate the effect of ulinastatin (UTI) and Taxotere(TXT) on tumor growth and expression of uPA, uPAR, p-ERK of transplantable tumor of MDA-MB-231 cell(ER-) in nude mice.Methods: Nude mice with transplantable tumor of MDA-MB-231 cell were given intraperitoneal injections in randomly divided 4 groups respectively: Control (Normal saline 200μl/day/mouse), UTI (1600u/day/mouse), TXT (10mg/7days/kg), UTI (1600u/day/mouse) + TXT (10 mg/7days/kg). Volume of the tumors are measured and noted for painting growth curve line. Twenty-one days after treatment, the mice were sacrificed, and the tumors were removed to make section of imm- unohistochemistry for examining expressing of uPA, uPAR and p-ERK.Results: When the experiment ended, a mouse dead respectively in group Control and UTI. During whole process, the volume of tumors were not reduced in group Control and UTI, the volume of tumors in group TXT and UTI+TXT were been reducing from the 13th day to the end. Ratio of inhibition: group UTI 29.312%, group TXT 86.021%, group UTI+TXT 98.264%. Expression of uPA, uPAR and p-ERK were all down-regulated by UTI, and up-regulated by TXT, the combination could also down-regulate the three proteins but less than single UTI.Conclusions: UTI could inhibit expression of uPA, uPAR and p-ERK in transplantable tumor of MDA-MB-231 cell, and may enhance anti-growth effect of TXT on tumor.