APN/CD13抑制剂乌苯美司:一个抗肿瘤化疗药物分子伴侣

APN/CD13 inhibitor Ubenimex:A molecular chaperone of antineoplastic chemotherapeutic drugs

细胞毒类抗肿瘤药物是目前治疗恶性肿瘤的主要手段之一,然而此类药物在杀死肿瘤细胞的同时,会对人体正常细胞(尤其是分裂增殖旺盛的细胞)产生毒副作用,其临床应用受到一定的限制。近年发现氨肽酶N抑制剂乌苯美司与抗肿瘤化疗药物有显著协同作用,能增强药物的治疗效果、减少化疗药物的毒副作用。该文概括了乌苯美司增强化疗药的抗肿瘤作用,通过抑制肿瘤干细胞自我更新、抑制自噬、诱导凋亡、增加宿主免疫力等途径逆转耐药的机制,论述了临床实验进展,进一步说明乌苯美司在治疗恶性肿瘤中可作为有效的辅助用药,为临床合理应用提供依据。

Cytotoxic anti-neoplastic drugs are a kind of chemotherapeutic drugs that directly kill or inhibit the growth and proliferation of tumor cells,and it is one of the main drugs for the treatment of malignant tumors.These drugs may have toxic side effects on normal cells of human body(especially those with strong division and proliferation)when they are used to kill tumor cells.And patients may usually have adverse reactions even at a normal dose when using this kind of drugs.Due to the strong toxic side effects of cytotoxic chemotherapeutic drugs,their clinical application is limited.In recent years it has been found that aminopeptidase N inhibitor Ubenimex has a significant synergistic effect with anti-neoplastic chemotherapeutic drugs,which has the advantages of enhancing the therapeutic effect of drugs and reducing the toxic side effects of chemotherapeutic drugs.This review enumerates that the combination of Ubenimex and a variety of cytotoxic drugs can enhance the anti-tumor effect of cytotoxic drugs and reduce the occurrence of adverse reactions.In addition,the mechanism of combined use of Ubenimex in reversing drug resistance is also introduced.At the same time,is is further confirmed the clinical value of Ubenimex as an effective adjuvant in the treatment of malignant tumors,so as to provide a basis for clinical application.