多药联合策略是提高肿瘤治疗效果的重要手段,是临床肿瘤治疗的主流方案。中药的有效成分,以蟾蜍皮和蟾蜍毒液为代表,具有效率高的优点,低毒性,广泛的作用和多靶点,近年来已成为肿瘤联合治疗策略的理想靶点。蟾蜍皮和蟾蜍毒液是来自BufobufogargarizansCantor或BufomelanosectictusSchneider的传统动物药物,在临床实践中作为辅助抗肿瘤药物对治疗各种癌症和癌症疼痛表现出优异的治疗效果。所涉及的机制包括诱导细胞凋亡,阻止细胞周期,抑制细胞增殖,移民和入侵,抑制肿瘤血管生成,逆转肿瘤细胞的多药耐药性,并调节多个信号通路和靶标。此外,基于纳米给药系统的多药联合策略可以实现蟾蜍皮或蟾蜍毒等抗肿瘤药物的活性成分的精确装载,携带药物克服生理和病理障碍,在肿瘤组织中完全有效富集,并实现对肿瘤细胞的靶向递送和药物的控释,从而增强抗肿瘤功效并减少毒性和副作用。本文就蟾蜍皮、蟾毒联合化疗药物的临床疗效和安全性进行综述。靶向药物,镇痛药和其他药物;评估蟾蜍皮肤和蟾蜍毒液联合化疗的效果和机制,靶向治疗,放疗或热疗,中药,细胞和动物模型中的信号通路抑制剂和其他疗法;并总结了蟾蜍皮和蟾蜍毒的活性成分与化疗药物的共同给药策略,小分子靶向药物,单克隆抗体,中药有效成分,以及光动力和光热治疗药物,为临床上合理使用蟾蜍皮和蟾蜍毒药物和新型给药系统的开发提供依据。
A multidrug combination strategy is an important mean to improve the treatment of cancer and is the mainstream scheme of clinical cancer treatment. The active ingredients of traditional Chinese medicine, represented by toad skin and toad venom, have the advantages of high efficiency, low toxicity, wide action and multiple targets and have become ideal targets in combined treatment strategies for tumors in recent years. Toad skin and toad venom are traditional Chinese animal medicines derived from Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider that have shown excellent therapeutic effects on the treatment of various cancers and cancer pain as adjuvant antitumor drugs in clinical practice. The involved mechanisms include inducing apoptosis, arresting the cell cycle, inhibiting cell proliferation, migration and invasion, inhibiting tumor angiogenesis, reversing the multidrug resistance of tumor cells, and regulating multiple signaling pathways and targets. Moreover, a multidrug combination strategy based on a nanodelivery system can realize the precise loading of the active ingredients of toad skin or toad venom and other antitumor drugs and carry drugs to overcome physiological and pathological barriers, complete efficient enrichment in tumor tissues, and achieve targeted delivery to tumor cells and the controlled release of drugs, thus enhancing antitumor efficacy and reducing toxicity and side effects. This article reviewed the clinical efficacy and safety of the combination of toad skin and toad venom with chemotherapeutic drugs, targeted drugs, analgesics and other drugs; evaluated the effects and mechanisms of the combination of toad skin and toad venom with chemotherapy, targeted therapy, radiotherapy or hyperthermia, traditional Chinese medicine, signaling pathway inhibitors and other therapies in cell and animal models; and summarized the codelivery strategies for the active ingredients of toad skin and toad venom with chemotherapeutic drugs, small-molecule targeted drugs, monoclonal antibodies, active ingredients of traditional Chinese medicine, and photodynamic and photothermal therapeutic drugs to provide a basis for the rational drug use of toad skin and toad venom in the clinic and the development of novel drug delivery systems.