化疗耐药可导致骨肉瘤治疗失败，逆转化疗耐药对骨肉瘤治疗具有重要意义。本课题组前期研究发现CD133+骨肉瘤干细胞具有显著化疗耐药性，改变NF-κB信号通路可影响MDR1的表达，进而降低其化疗耐药，但该机制的上游靶点尚不清楚。最新研究发现微管亲和调节激酶2（MARK2）与NF-κB通路呈负相关，在DNA损伤修复和细胞周期激活中发挥重要作用，我们已发现顺铂刺激可引起骨肉瘤MG63细胞系中MARK2在 mRNA水平的显著升高，但MARK2在骨肉瘤化疗耐药中的作用及其具体机制尚不明了。本课题研究MARK2在骨肉瘤肿瘤干细胞化疗耐药中的作用，探讨其与NF-κB通路的关系，并通过体内实验验证干预MARK2后骨肉瘤细胞致瘤性及耐药性的变化，为逆转骨肉瘤化疗耐药提供新的思路。

Drug resistance is the important reason for the failure of therapy for osteosarcoma. We previously found that CD133+ osteosarcoma CSCs displayed drug resistance, which could be reversed targeting MDR1 through NF-κB pathway. But the upstream mechanism in osteosarcoma is still unclear. MARK2 was recently found had close relationship with NF-κB pathway, and played an important role in DNA damage repair and cell cycle, the relationship between MARK2 and drug resistance of osteosarcoma is still unknown. We intend to study the role of MARK2 in chemoresistance of osteosarcoma and its relationship with NF-κB pathway in osteosarcoam stem cells, and to study the oncogenicity and drug resistance in tumor-bearing mice targeting MARK2, for the purpose of finding a new method to reverse the chemoresistance in osteosarcoma therapy.