Liu Wei,Zhao Zhenzhen,Zhao Lihua,Jin Xianqing.Transplantation of hMDR1-transferred bone marrow mononuclear cells and chemotherapy in breast cancer xenograft in mice[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(15):1551-1554.
Liu Wei,Zhao Zhenzhen,Zhao Lihua,Jin Xianqing.Transplantation of hMDR1-transferred bone marrow mononuclear cells and chemotherapy in breast cancer xenograft in mice[J].J Amry Med Univ (J Third Mil Med Univ),2011,33(15):1551-1554.DOI:
Transplantation of hMDR1-transferred bone marrow mononuclear cells and chemotherapy in breast cancer xenograft in mice
Objective To determine the myeloprotection and therapeutic effects of transplantation of human multidrug resistance gene 1 (hMDR1)-transferred mononuclear cells (MNCs) on over-dosage chemotherapy to the mice with 4T1 xenograft breast cancer. Methods Primary MNCs isolated from bone marrow of BALB/c mice were transfected with a replication-deficient recombinant adenovirus expression vector carrying hMDR1 and GFP (rAd-hMDR1-GFP) to obtain hM
DR1-modified MNCs (MNCs-rAd-hMDR1-GFP). The transfected and nontransfected cells were then transplanted into BALB/c mice with 4T1 breast cancer xenograft and over-dose epirubicin (15 mg/kg
once a week). The xenograft mice without any treatment (control)
with normal dose epirubicin (5 mg/kg
once a week) and with over-dose epirubicin served as control. The chemoprotection effects of hMDR1 gene for the hematopoietic bone marrow and effectiveness of over-dose chemotherapy were assessed. Results MNCs were transfected with the vector rAd-hMDR1-GFP in vitro with a transfection rate of 26.26%. After transplantation
the expression of hMDR1 gene
which confers chemoprotection
was confirmed. The mouse with 4T1 breast cancer xenograft could tolerate the 3 times higher than the usual dose of epirubicin and the leukocytes count in peripheral blood was maintained at (5.7±0.6)×10
9
/L. Over-dose chemotherapy reduced the breast cancer cells dramatically and extended the survival time of mouse (P0.05). Conclusion Transplantation of hMDR1 transfected bone marrow hematopoietic cells increases the tolerance of xenograft to chermotherapy and improves the therapeutic effect of chemotherapy to the tumor.
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