宫颈癌是女性最常见的恶性肿瘤之一。化疗是中晚期宫颈癌重要的治疗措施。基于紫杉醇的联合化疗是中晚期宫颈癌患者的主要疗法。宫颈癌细胞对紫杉醇产生耐药是治疗失败的主要原因。宫颈癌紫杉醇耐药的机制尚不明确。既往研究紫杉醇耐药相关的ABC转运蛋白中多未提及ABCC5，且针对ABC转运蛋白家族的靶向调控并不能很好的逆转耐药。FOXM1是引起紫杉醇化疗耐药的重要转录因子，但其具体机制、转录结合位点不详。前期研究已揭示紫杉醇耐药的细胞株中FOXM1、ABCC5高表达。结合文献报道ABCC5可被特异性抑制FOXM1转录的硫链丝菌素抑制，在其启动子区存在FOXM1的结合位点，上述均提示FOXM1可能调控ABCC5转录致细胞流出药物增多而发生紫杉醇耐药。本课题拟明确FOXM1调控ABCC5转录的机制，证实靶向FOXM1或同时靶向FOXM1和ABCC5能逆转紫杉醇耐药，为化疗耐药的宫颈癌患者靶向治疗提供依据。

Cervical cancer is one of the most common malignant tumors in women.Chemotherapy are important for the treatment of locally advanced cervical cancer.Based on paclitaxel combination chemotherapy is the main therapy in patients with locally advanced cervical cancer. Drug resistance is the main cause of cervical cancer treatment failure. The mechanism of paclitaxel resistance in cervical cancer is not clear.In previous studies, the ABCC5 was not mentioned in ABC transporters related to paclitaxel resistance, and the targeted regulation of ABC transporter family was not a good reversal of drug resistance.FOXM1 is an important transcription factor that causes the drug resistance of paclitaxel, but the specific mechanism and transcriptional binding site are unknown.Earlier research has revealed that FOXM1, ABCC5 were high expression in paclitaxel resistance cell lines. In combination with the literatures reported that ABCC5 can be inhibited by thiostrepton,which specifically inhibit the transcription of FOXM1, its promoter region exist FOXM1 binding sites, so suggest that FOXM1 induced drug resistance by regulating abcc5 gene transcription and drug efflux in cervical cancer cells.This topic aims to found the mechanism of FOXM1 regulating abcc5 gene transcription,targeting FOXM1 or simultaneously targeting FOXM1 and ABCC5 could overcome paclitaxel drug resistance, provide the basis for target therapy of cervical cancer chemoresistance.