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A recombinant protein TmSm(T34A) can inhibit proliferation and proapoptosis to breast cancer stem cells(BCSCs) by down-regulating the expression of Cyclin D1
Affiliation:1. Laboratory of Cytogenetics and Molecular Diagnostics, Division of Cancer Research, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India;2. Division of Medical Oncology, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India;3. Division of Cancer Epidemiology and Biostatistics, Regional Cancer Centre, Medical College Post, Trivandrum 695011, Kerala, India;4. Department of Biochemistry, PSG College of Arts and Science, Civil Aerodrome Post, Coimbatore 641014, India
Abstract:Cancer stem cells (CSCs), a small fraction of cancer cells lines proved with stem cell characteristics, were regarded as “bad seeds” related to recurrence, metastasis and chemotherapy resistance of breast carcinoma in recent years. So inhibiting the growth or inducing the differentiation and apoptosis of CSCs were considered as one of the effective pathways to fight against breast cancer. Based on the recombinant protein TmSm(T34A) that was designed and prepared in our previous experiments for targeting survivin, an inhibitor of apoptosis protein(IAP), in this study, we explored the effects of TmSm(T34A) on BCSCs obtained by enriching in serum-free suspension, sorting and characterizing of MCF-7/ADM. The results showed that TmSm(T34A) could not only inhibit the proliferation and growth of BCSCs by decreasing CD44+CD24 proportion and down-regulating the expression of Cyclin D1 significantly, but also induce BCSCs apoptosis evidently. Furthermore, in BCSCs xenograft nude mice administrated TmSm(T34A), the tumor growth was slower than that of the control obviously. Thus it can be seen TmSm(T34A) would be a promising potential protein for treatment of breast cancer by effecting on BCSCs.
Keywords:TmSm(T34A)  BCSCs  Proliferation  Proapoptosis  Cyclin D1
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