Wang Yi, Jin Xian-Qing, Wang Shan, Wang Qiao, Luo Qing, Luo Xiao-Ji
Department of General Surgery, Chongqing Children's Hospital, Chongqing University of Medical Sciences, Chongqing 400014, China.
Hepatobiliary Pancreat Dis Int. 2006 Nov;5(4):545-51.
Malignant tumors are common diseases threatening to the health and life of human being. Clinically, the multidrug resistance of tumor cells and bone marrow depression caused by chemotherapeutic agents are the main obstacles to the treatment of tumors, and both are related to the mdr1 gene. The over expression of the mdr1 gene in tumor cells contributes to the multidrug resistance of malignant tumor cells. With little expression of the mdr1 gene, bone marrow cells particularly susceptible to multidrug resistance-sensitive agents, which cause serious toxicity in bone marrow. This study was undertaken to assess therapeutic efficacy of transplantation of bone marrow mononuclear cells transferred with the mdr1 gene and over-dose chemotherapy with doxorubicin for VX2 hepatocarcinoma of rabbits.
The mdr1 gene was transferred into the bone marrow mononuclear cells of rabbits, which was co-cultured with retroviral vector-containing supernatant, and the cells were autotransplanted into a rabbit model with VX2 hepatocarcinoma. After chemotherapy with doxorubicin, the protective effects of the mdr1 gene and therapeutic efficacy of over-dose chemotherapy were observed.
The mdr1 gene was transferred successfully into the bone marrow mononuclear cells, with a transduction efficiency of 35%. After autotransplantation, the mdr1 gene was expressed functionally in bone marrow with a positive rate of 8%, indicating that the gene played an important role in bone marrow protection. The rabbits with VX2 hepatocarcinoma, which had received the mdr1 gene-transduced cells, survived after chemotherapy with a 3-fold dose of adriamycin, and their white blood cell counts were (4.26 +/- 1.03) x 10(4)/L. Since hepatocarcinoma cells were eradicated, the survival time (97.00 +/- 46.75 d) of the rabbits was extended (P<0.05) and the healing rate of the tumor was increased (P<0.05).
The transferring of the mdr1 gene into bone marrow mononuclear cells could confer chemoprotection to bone marrow, and over-dose chemotherapy could be prescribed for the treatment of malignant tumors.
恶性肿瘤是威胁人类健康和生命的常见疾病。临床上，肿瘤细胞的多药耐药性以及化疗药物引起的骨髓抑制是肿瘤治疗的主要障碍，二者均与mdr1基因有关。mdr1基因在肿瘤细胞中的过度表达导致恶性肿瘤细胞产生多药耐药性。mdr1基因表达较少时，骨髓细胞对多药耐药性敏感药物特别敏感，这会在骨髓中引起严重毒性。本研究旨在评估转染mdr1基因的骨髓单个核细胞移植联合阿霉素过量化疗对兔VX2肝癌的治疗效果。
将mdr1基因转入兔骨髓单个核细胞，与含逆转录病毒载体的上清液共培养，然后将细胞自体移植到VX2肝癌兔模型中。给予阿霉素化疗后，观察mdr1基因的保护作用及过量化疗的治疗效果。
mdr1基因成功转入骨髓单个核细胞，转导效率为35%。自体移植后，mdr1基因在骨髓中功能性表达，阳性率为8%，表明该基因在骨髓保护中起重要作用。接受转染mdr1基因细胞的VX2肝癌兔，在接受3倍剂量阿霉素化疗后存活，其白细胞计数为(4.26±1.03)×10⁴/L。由于肝癌细胞被根除，兔的生存时间(97.00±46.75 d)延长(P<0.05)，肿瘤治愈率提高(P<0.05)。
将mdr1基因转入骨髓单个核细胞可赋予骨髓化学保护作用，可采用过量化疗治疗恶性肿瘤。
