Effect Of Ulinastatin And Cyclophosphamide On CXCR4 Expression And Proliferation Of Breast Cancer

PARTⅠEFFECT OF ULINASTATIN ON CXCR4 EXPRESSION, PROLIFERATION INDUCED BY CYCLOPHOSPHAMIDE IN BREAST CANCER CELL LINE MDA-MB-231 AND MCF-7Objective:To observe the effect of ulinastatin(UTI) on matrix CXCR4 expression,proliferation and chemotaxis induced by cyclophosphamide(CTX) in breast cancer cell line MDA-MB-231 and MCF-7.And to detect the relationship of chemotatic factor receptor CXCR4 and breast cancer.Methods:The breast cancer cell line MDA-MB-231 and MCF-7 were randomly divided into eight groups:UTI low dose,UTI low dose,UTI middle dose,UTI high dose,CTX,UTI low dose+CTX,UTI middle dose+ CTX,UTI high dose+CTX and blank control group.The expression of CXCR4 was detected by reverse transcription and quantitative real-time polymerase chain reaction(Real time RT-PCR).The cell proliferation was analyzed by the MTT assy.And the chemotaxis of SDF-1 to the breast cancer was analysed by Transwell plate.Results:The expression of CXCR4 in MDA-MB-231 and MCF-7 cells was down-regulated and the invasion ability of which was decreased after the treatment.Compared with the control group,the UTI significantly inhibited the proliferation of both ER-positive MCF-7 and ER-negative MDA-MB-231 cells induced by CTX in a dose-dependent pattern. Compared with the CTX group,the inhibition effect on the proliferation was weaker,but the inhibitory efficient of UTI combined with CTX was higher than that of CTX used alone.And the level of CXCR4 s expression was closely correlated to cancer metastasis.Conclusion:UTI has a synergetic effect on cell apoptosis induced by CTX in in breast cancer cell line MDA-MB-231 and MCF-7,the down-regulation of CXCR4 expression may be one of the main mechanisms. PARTⅡEFFECT OF ULINASTATIN ON CXCR4 EXPRESSION, PROLIFERATION AND INVASION INDUCED BY CYCLOPHOSPHAMIDE IN BREAST CANCER MICEObjective:To investigate whether UTI and CTX inhibit tumor invasion and metastasis of breast cancer mice.And to observe the effect of ulinastatin(UTI) on matrix CXCR4 expression,proliferation induced by cyclophosphamide(CTX) in breast cancer mice.Methods:Subcutaneous(s.c.) implantation of MCF-7 in the right subcutaneous armpit of nu/nu mice.There were forty mice divided into eight groups with random.There were physiological saline group,CTX group,UTI low dose group,or UTI low dose group or UTI middle dose group,or UTI high dose group,or UTI low dose+CTX group,or UTI middle dose+CTX group,or UTI high dose+CTX group.They all started injecting into abdominal cavity at the sixth day.The weight of primary tumor was established by the 14th day after tumor cell inoculation. Expression of CXCR4 was detected by reverse transcription and quantitative real-time polymerase chain reaction(Real time RT-PCR).The above-mentioned result was checked by immunity class.Results:Compared with the control group,the UTI significantly inhibited the growth of subcutaneous tumor.Compared with the CTX group,the inhibition effect on the growth of subcutaneous tumor was weaker,but the inhibitory efficient of UTI combined with CTX was higher than that of CTX used alone.The average weight of subcutaneous tumor in turn were(6.95±2.56,4.19±1.34,4.92±1.08,5.36±1.19,3.86±1.73,0.87±0.50,1.93±0.96 and 2.25±1.45).Conclusion:UTI can inhibit the breast cancer,compared with the CTX the inhibition effect on the breast cancer has a synergetic effect on cell was weaker,but the inhibitory efficient of UTI combined with CTX was higher than that of CTX used alone.