摘要
恶性肿瘤通过多种机制产生肿瘤耐药。细胞自噬是在生理条件和病理条件下普遍存在的生理机制,不仅能参与维持细胞稳态,还与肿瘤的发生发展和肿瘤耐药密切相关。化疗药物通过抑制磷脂酰肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白(phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin,PI3K-Akt-mTOR)信号通路、活化单磷酸腺苷活化蛋白激酶(AMP-activated protein kinase,AMPK)抑制mTOR激酶活性、诱导Beclin 1/Bcl-2复合物解耦联等途径,诱导肿瘤细胞自噬,影响肿瘤细胞对化疗药物敏感性。因此,抑制细胞自噬是对抗肿瘤耐药的潜在途径,抑制肿瘤细胞自噬联合化疗药物的应用,有望成为有效的肿瘤治疗策略。
Malignant tumors resist chemotherapy drugs through a variety of mechanisms. As a general physiological mecha- nism under both physiological and pathological conditions, autophagy can not only take part in maintaining homeostasis, but also be closely related with tumor development and resistant. Autophagy can be induced by chemotherapy agents through several ways in cancer cells, such as inhibiting P13K-Akt-mTOR pathway, activating AMPK-mTOR pathway and inducing dissociation of Beclinl/Bcl-2 com- plex, which exerts an effect on the chemosensitivity. Therefore, autophagy is a potential target for antitumor drug resistant. Specific in- hibition of autophagy in cancer cells combined with chemotherapy is expected to be an effective cancer treatment strategy.
出处
《医学研究生学报》
CAS
北大核心
2012年第12期1302-1307,共6页
Journal of Medical Postgraduates
基金
国家自然科学基金(81071806
81172106)
江苏省自然科学青年基金(BK2012371)
关键词
自噬
凋亡
肿瘤
化疗
耐药
Autophagy
Apoptosis
Cancer
Chemotherapy
Resistance
