Effect Of Ulinastatin And Taxotere On Proliferation,invasion,Apoptosis Of Human Breast Cancer Cell And Expression Of IGF-1R, PDGFA And PAFR

PART 1 EFFECT OF ULINASTATIN AND TAXOTERE ON PROLIFERATION,INVASION,APOPTOSIS AND ON PAFR,PDGFA AND IGF-1R EXPRESSION OF PRIMARY HUMAN BREAST CANCER CELLObjective: To explore the synergistic effects of ulinastatin(UTI) and Taxotere(TXT) on proliferation,apoptosis and invasion of primary human breast cancer cell, as well as expression the PAFR, PDGFA, IGF-1R.Methods: The primary human breast cancer cell were divided into 4 groups: control group, UTI group, TXT group, UTI+TXT group (including UTI, 800UI/ml; TXT, 3.7μg/ml). The inhibitory effect of UTI and TXT on the cell proliferation and invasion of primary human breast cancer cell were detected by the MTT and Transwell assay, the effect of UTI and TXT on the cell apoptosis were detected by the Flow Cytometry (FCM). And then, the RNA and protein expressions of PAFR, PDGFA and IGF-1R were analyzed by Western Blot and RT-PCR.Results: The combination of ulinastatin and Taxotere synergistically decreased the cell proliferation and invasion of primary human breast cancer cell compared with control group and single medication group, as well as induced the cell apoptosis. Western Blot and RT-PCR results showed that the PAFR,PDGFA and IGF-1R expressions were significantly inhibited.Conclusions: UTI enhanced the inhibitory effect on proliferations of primary human breast cancer cell induced by TXT. Meanwhile, UTI showed synergistic effect with TXT by a potential mechanism of decreasing the expression of IGF-1R, PDGFA and PAFR. PART 2 EFFECT OF ULINASTATIN AND TAXOTERE ON TUMOR GROWTH AND EXPRESSION OF PAFR,PDGFA AND IGF-1R IN BREAST CANCER XENOGRAFT MODELSObjective: To investigate the effect of UTI and TXT on tumor growth and expression of PAFR, PDGFA and IGF-1R of human breast carcinomas in nude mice.Methods: Nude mice which injected with primary breast cancer cell in randomly were divided 4 groups: Control (Normal 200μl/day/mice), UTI (1600UI/day/mice), TXT (20mg/7days/kg), UTI (1600UI/day/mice) + TXT (20mg/7days/kg). Tumors Volume were measured and noted for growth curve every 3 days. Three weeks after treated, the all mice were sacrificed, the expression of PAFR, PDGFA and IGF-1R were measuring by immunohistochemistry.Results:UTI group could not decrease tumor volume, but can delay the increase of tumor volume in the tumor growth curves. Two weeks after grafting, TXT and UTI + TXT group gradually reduced tumor volume, inhibition rate: TXT 88.44%,UTI + TXT 97.82%. Compared with the control group, UTI and TXT can significantly down-regulate the protein expression of PAFR, PDGFA, IGF-1R (p <0.05), and the inhibition effect were UTI + TXT group> TXT group> UTI group (p <0.05). Conclusions: UTI and TXT could inhibit the growth of tumour and down-regulate the expression PAFR, PDGFA and IGF-1R of breast cancer xenografts tumors, UTI could enhance the synergistic effect of TXT.