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The Role and Mechanism of RABEX-5Signaling Pathway in Breast Cancer Proliferation and Metastasis

Author: ZhangXiang
Tutor: LiHongYuan
School: Chongqing Medical University
Course: Surgery
Keywords: RABEX-5 breast cancer chemotherapy sensitivity MMP-9
CLC: R737.9
Type: Master's thesis
Year: 2013
Downloads: 9
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Abstract


Objective:To observe the effect of RABEX-5downregulation inproliferation and metastasis of breast cancer cells in vitro andtumorigenicity in vivo. And to investigate the changes in sensitivity ofanthracycline and taxanes in human breast cancer cells after RABEX-5downregulation.Methods:Two stable cell lines were established, namely, MCF-7/KD,which downregulated RABEX-5expression using RNA interference(RNAi),and MCF-7/NC as a negative control. The colony formation assayand the wound healing assay were used to explore the ability of RABEX-5to cell proliferation and metastasis in breast cancer cells, respectively. Thechanges in sensitivity to chemotherapeutic drugs of MCF-7/KD and itsnegative control cell lines MCF-7/NC were detected by cck-8. In vivo,studies were conducted in immunodeficient mice. The effect of RABEX-5downregualation to proliferation、 metastasis and the expression ofassociated signaling molecules of breast cancer were further verified.Results: RABEX-5silencing significantly reduced cancer cell proliferation, colony formation and migration ability in vitro and inhibitedtumor growth in vivo. RABEX-5knockdown also attenuated migration ofbreast cancer cells via modulation of MMP-9transcriptional activities. Thesensitivity to epirubicin was reduced after downregulating the expression ofRABEX-5, the50%inhibition concentration (IC50) of MCF-7/KD(3.5900±0.22869μg/ml) was higher than that of MCF-7/NC(1.1933±0.18771μg/ml)(P<0.05); while the same effect was not found indocetaxel group, the IC50were11.1627±0.21026μg/ml and10.5367±0.43097μg/ml,respectively(P>0.05).Conclusion:Downregulation of RABEX-5can reduce theproliferation and metastasis potential of breast cancer and inducechemoresistance to epirubicin in human breast cancer cell MCF-7; while itseffect on sensitivity to docetaxel is not significant. This study can provide atheoretical basis for future research RABEX-5in the individualizedtreatment of breast cancer.

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CLC: > Medicine, health > Oncology > Genitourinary tumors > Breast tumor
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