γ-Tocotrienol-NF-κB-P-gp调控轴在逆转乳腺癌多药耐药中的作用机制研究

肿瘤多药耐药现象是癌症治疗领域的难题。γ-Tocotrienol，作为维生素E家族的主要成员之一，与抗癌药物联合使用可以降低抗癌药物的使用浓度、毒性反应以及机体副反应程度，但此协同效应的具体分子机制尚未完全明确。本课题在前期发现γ-tocotrienol可以增加乳腺癌耐药细胞MCF7/Adr的药物敏感性并降低ABC转运体P-糖蛋白（P-gp）表达的基础上，进一步探讨γ-tocotrienol调控NF-κB信号途径的方式（抗氧化依赖or非抗氧化依赖），以及通过NF-κB调控P-gp表达的分子机制，并以此为切入点，关注γ-tocotrienol-NF-κB-P-gp调控轴在乳腺癌多药耐药及药物协同效应中的调节机制。本项目研究成果将为γ-tocotrienol作为辅助药物协同参与癌症治疗提供理论依据，同时也为γ-tocotrienol调节肿瘤细胞多药耐药的逆转机制提供新的视角。

The problem of multidrug resistance (MDR) presents a major obstacle in the chemotherapy of cancer. Tocotrienols, the vitamin E of the 21st century, is often given in combination with other chemotherapeutic agents in cancer therapy. The synergistic effect mediated by γ-tocotrienol reduces the dosage of chemotherapeutic agents and eliminates the likelihood of adverse and toxic side effects. However, the exact mechanism of the synergistic effect played by γ-tocotrienol remains still unknown. In our previous study, we found that γ-tocotrienol could enhance the sensitivity of breast cancer cells (MCF7/Adr) to other chemotherapeutic agents and decrease the expression of P-glycoprotein (P-gp). Furthermore, we will study the mechanism how NF-κB regulate the expression of P-gp, and which pathway (anti-oxidant dependent or independent) do γ-tocotrienol mediate to regulate the NF-κB transcription activity. Ultimately, we will demonstrate the synergistic effect of γ-tocotrienol-NF-κB-P-gp axis on multi-drug resistance of breast cancer. The study would provide a theoretical basis for γ-tocotrienol acting as an adjuvant in cancer therapy, and elucidate the mechanism of multidrug resistance reversed by γ-tocotrienol from a new optic angle.