Department of General Surgery, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, China.
Department of Oncology, Jing'an District Central Hospital of Shanghai, Fudan University, Shanghai, 200040, China,
Front Biosci (Landmark Ed). 2019 Jan 1;24(2):303-312. doi: 10.2741/4719.
Oxaliplatin is one of the most common chemotherapy drugs for colorectal cancer (CRC), but its application is greatly limited owing to the drug resistance. Nobiletin is a natural flavonoid isolated from citrus peel and has many biological functions, including anti-inflammatory, antitumor and neuroprotective activities. However, little is known about the effect of nobiletin on the anti-tumor activities of other chemotherapy drugs. In this study, we examined the effect of nobiletin on the efficacy of oxaliplatin in treatment of CRC by using two CRC cell lines. experiments indicated that nobiletin enhanced the inhibitory effect of oxaliplatin on the proliferation of CRC cells. Meanwhile, nobiletin promoted oxaliplatin-induced apoptosis of CRC cells, as demonstrated by the increased expression of pro-apoptotic proteins (Bax and cleaved-caspse3) and the down-regulation of anti-apoptotic protein Bcl-2. Mechanically, nobiletin sensitized CRC to oxaliplatin chemotherapy by down-regulating the PI3K/Akt/mTOR pathway. Taken together, our study has demonstrated that nobiletin could enhance the sensitivity of CRC to oxaliplatin chemotherapy, and provided a molecular basis for nobiletin's potential applications in the chemosensitization of CRC.
奥沙利铂是结直肠癌（CRC）最常用的化疗药物之一，但由于耐药性，其应用受到极大限制。诺必灵是从柑橘皮中分离得到的一种天然黄酮类化合物，具有多种生物学功能，包括抗炎、抗肿瘤和神经保护作用。然而，关于诺必灵对其他化疗药物的抗肿瘤活性的影响知之甚少。在这项研究中，我们使用两种 CRC 细胞系研究了诺必灵对奥沙利铂治疗 CRC 疗效的影响。实验表明，诺必灵增强了奥沙利铂对 CRC 细胞增殖的抑制作用。同时，诺必灵促进奥沙利铂诱导的 CRC 细胞凋亡，表现为促凋亡蛋白（Bax 和 cleaved-caspse3）表达增加和抗凋亡蛋白 Bcl-2 下调。机制上，诺必灵通过下调 PI3K/Akt/mTOR 通路使 CRC 对奥沙利铂化疗敏感。综上所述，本研究表明诺必灵可增强 CRC 对奥沙利铂化疗的敏感性，为诺必灵在 CRC 化学增敏中的潜在应用提供了分子基础。
