中西医结合分子配伍治疗肿瘤协同增效及逆转耐药的研究进展

Research progress on molecular compatibility in integrated Chinese and Western medicine to foster synergy and reverse resistance of cancer cells to anticancer drugs

增效减毒是中西医结合治疗肿瘤的特色和优势,如何有效增强抗肿瘤药物的敏感性或逆转其耐药性已成为当今肿瘤治疗亟待解决的问题。传统中医药主要通过发挥多组分、多靶点、多阶段的优势而具有增强抗肿瘤药物敏感性或逆转肿瘤耐药的功效,但其成分复杂,具体机制尚未明确。现代医学克服肿瘤耐药的主要策略为更换新一代药物,但这些药物靶点相对单一、不良反应较多,且容易诱发多药耐药,因而限制了其在肿瘤治疗中的广泛应用。本课题组在传统中医药配伍理论“君臣佐使”“七情和合”的基础上,研究了具有化疗增敏和逆转耐药作用的中药,挖掘出其发挥药效的有效成分,阐明了其发挥作用的分子机理,进一步将成分、结构、药效、机理清楚的多个活性分子与抗肿瘤药物优化配伍,组成新的“分子配伍”复方,形成药效叠加、不良反应减小的“分子配伍”药物,为增强抗肿瘤药物的疗效提供了一种中西医结合“分子配伍”的治疗策略。本文将系统性阐述中西医结合“分子配伍”的科学内涵,分析其在治疗肿瘤协同增效和抑制耐药方面的研究现状,以期为肿瘤治疗提供一种新的方法和策略。

The advantages of combining traditional Chinese medicine(TCM)and western medicine for treating tumors include enhancement of treatment efficiency and reduction of toxicity.The resistance of cancer cells to anticancer drugs remains a critical issue in cancer treatment.TCMs have the ability to increase the sensitivity of cancer cells to anticancer drugs and overcome drug resistance through their multi-component,multi-target,and multi-stage mechanisms.However,the components are complex and the specific mechanisms are unclear.To overcome drug resistance,modern medicine advocates the replacement of anticancer agents with those of a new generation.However,these drugs often have single targets,result in greater side effects,and easily induce multidrug resistance,which limits the efficacy of anticancer treatment.Based on the compatibility theory of TCM,"Jun-Chen-Zuo-Shi,"we studied several Chinese medicines with a chemotherapeutic sensitization effect and the ability to reverse drug resistance.Additionally,we extracted their effective ingredients and determined their possible molecular mechanisms.Furthermore,multiple active molecules with clear ingredients,structure,efficacy,and mechanism were optimized to form a compound with"molecular compatibility"and the ability to generate a synergistic anticancer effect,decrease the dose of each individual compound,reduce individual drug-related toxicity,and suppress multidrug resistance through different mechanisms.Understanding the scientific connotation of"molecular compatibility"by combining TCM and western medicine would provide a new strategy for overcoming cancer drug resistance.