细胞色素P4503A4与肿瘤化疗耐药的关系研究进展

Research Progress of Relationship between Cytochrome P4503A4 and Tumor Chemotherapy Resistance

恶性肿瘤仍是目前威胁人类健康的重大疾病之一,化疗过程中肿瘤细胞对化学药物产生耐药性是抗肿瘤化疗失败的重要因素,严重影响患者预后及生存,明确影响肿瘤化疗耐药性的因素十分重要。细胞色素P450(CYP450)氧化代谢酶系是参与化疗药物代谢过程的关键酶之一,与多数抗肿瘤药物的生物转化、代谢消除密切相关,其中CYP4503A4(CYP3A4)是CYP450家族最重要的药物代谢酶。其可以降低和清除具有细胞毒性的化疗药物的毒性,部分抗癌前药经CYP3A4代谢后具有更强的抗肿瘤活性。其在肿瘤化疗耐药中占据重要位置,深入研究CYP3A4在肿瘤病理机制、疾病进展、预后生存中的作用,对肿瘤的防治具有重要价值。

Malignant tumors are still one of the major diseases threatening human health,and the resistance of tumor cells to chemical drugs during chemotherapy is an important factor in the failure of anti-tumor chemotherapy,which seriously affects the prognosis and survival of the patients,so it is critical to clarify the factors that affect tumor chemotherapy resistance.Cytochrome P450(CYP450)oxidative metabolism enzyme system is one of the key enzymes involved in the metabolism of chemotherapeutic drugs,and is closely related to the biotransformation and metabolic elimination of most anti-tumor drugs,among them,CYP4503A4(CYP3A4)is the most important drug metabolism enzyme in the CYP450 family.It can reduce and clear the toxicity of chemotherapy drugs with cytotoxicity,some anti-cancer prodrugs have stronger anti-tumor activity after their metabolism by CYP3A4.It plays an important role in tumor chemotherapy resistance.In-depth study of the role of CYP3A4 in tumor pathology,disease progression,and prognostic survival is of great value for tumor prevention and treatment.