化疗是治疗恶性滋养细胞肿瘤有效的方法，然而对化疗耐药仍是目前恶性滋养细胞肿瘤临床治疗的主要瓶颈，约20%的患者最终因化疗耐药而死亡。本课题组前期工作中，我们发现绒癌耐药与内质网应激及自噬密切相关，但是绒癌耐药和内质网应激及自噬的关系国内外迄今无相关报道。预实验中我们观察到耐药绒癌JNK/P62信号通路上调，我们推测该通路可能参与耐药绒癌的发病机制，其机制涉及内质网应激介导的凋亡和自噬。为证实这个假说，该课题拟通过抑制自噬和凋亡的方法明确明确自噬在耐药绒癌中的作用，从细胞水平和动物水平进一步研究JNK/P62信号通路对内质网应激介导凋亡和自噬的调节作用和调控途径，探讨绒癌耐药的发生机制，为耐药绒癌的靶向治疗提供理论依据。

Gestational trophoblastic neoplasia (GTN) is one of the most highly curable forms of adult malignancy, largely due to the exceptional sensitivity of this tumor to chemotherapy. However, approximately 20% of patients with multidrug resistance will still fail treatment and die. This is emphasizes the necessity to find a new approach for the treatment of these patients with high risk. According to our previous investigation in the study of drug-resistance choriocarcinoma, we recognized that endoplasmic reticulum (ER) stress and autophagy might be associated with drug resistance of choriocarcinoma, which was not reported in the published literatures. We also found that the JNK/P62 signal pathway upregulated in drug resistance choriocarcinoma cell lines. We presumed that JNK/P62 signal pathway was related to drug resistance of choriocarcinoma. The mechanism of JNK/P62 pathway is involved in regulating endoplasmic reticulum stress induced apoptosis to autophagy switch. Therefore, the effect of autophagy will be investigated in drug-resistant choriocarcinoma by inhabitation of autophagy and apoptosis in our study. Then we would explore the mechanism of JNK/P62 signal pathway both in vitro and in vivo, which might play the protective role via attenuating ER stress-induced apoptosis and boosting autophagy switch. We think that we are presenting an attractive stand-alone anticancer strategy as well as an opportunity to enhance the efficacy of current chemotherapeutic agents in drug-resistant choriocarcinoma.