TLR4/MyD88信号通路在卵巢癌紫杉醇化疗抵抗中的研究进展

Research progress on TLR4/MyD88 signaling pathway in paclitaxel- resistant ovarian carcinoma

妇科恶性肿瘤是危害妇女健康的重要疾患之一。卵巢癌作为恶性程度最高、死亡率居第一位的妇科恶性肿瘤,70%-80%的患者在初次就诊时已经是Ⅲ～Ⅳ期,尽管现在治疗方法不断改善,仍有80%的卵巢癌患者在1～2年内复发,国际妇产科联盟(FIGO)临床分期Ⅳ期卵巢癌患者的5年总体生存(OS)率<5%。有研究显示,作为免疫源性肿瘤的卵巢癌,其一线用药紫杉醇有效率仅为30%。紫杉醇是TOLL样受体4(TLR4)的主要配体之一,TLR4在卵巢组织中均有表达,在恶性肿瘤细胞中的染色强度明显增高,MyD88在卵巢癌组织中的表达率为77.1%,但在正常卵巢上皮组织中却不表达,MyD88的高表达是影响卵巢癌患者无瘤生存期与总生存期的独立预后因素。对MyD88阳性的卵巢上皮癌患者,TLR4/MyD88信号通路激活后,能通过促进各类炎症细胞因子增殖、抑制癌细胞凋亡及抑制免疫功能三个方面导致紫杉醇化疗抵抗和复发,甚至促进癌细胞增殖。

Gynecological malignancies are one of the important diseases endangering women's health.Ovarian cancer is the most malignant tumour, ranking first in gynecological malignancy death.About 70%-80% of the patients are diagnosed as stage III-IV at their initial visit.Although the treatment methods are ever improving and updating, 80% of the ovarian cancer patients still have a recurrence within one to two years, and the 5-year total survival rate in patients with stage IV ovarian cancer according to International Federation of Gynecology and Obstetrics (FIGO) staging criteria is less than 5%.Studies have shown that paclitaxel, a first-line treatment for immunogenic ovarian cancer, is only30% effective.Paclitaxel is one of the main ligands of toll-like receptor 4 (TLR4).TLR4 is expressed in all ovarian tissues, and its staining intensity is significantly increased in malignant tumor cells.MyD88 expression is observed in 77.1 % ovarian tissues, but not expressed in normal ovarian epithelial tissues, so the high expression of MyD88 is an independent prognostic factor for tumor-free survival and total survival of ovarian carcinoma patients.In epithelial ovarian carcinoma patients with positive MyD88, the activation of TLR4/MyD88 -dependent pathway mediates chemoresistance and tumor progression by inflammatory cytokine stimulation, apoptosis inhibition, and immunosuppression, and even promotes cancer cell growth.