Zhu Xingyao, Zhang Ruiqi, Liu Yuhua, Yang Caiyun, Ding Qi, Gu Wenyi, Zou Hong
Department of Pathology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang, 310009, China.
Department of Pathology, The First Affiliated Hospital, Shihezi University School of Medicine, Xinjiang, 832002, China.
Sci Rep. 2025 May 9;15(1):16217. doi: 10.1038/s41598-025-94620-y.
Colorectal cancer is one of the most common malignant tumors, and its drug resistance poses a huge challenge and a serious threat to people's health. In previous studies, we have found that the combination of paclitaxel and BEZ235 has synergistic anti-colon cancer effects, particularly in drug-resistant colorectal cancer, demonstrating excellent anti-tumor effects. Therefore, this study aims to investigate the preparation of the nanoemulsification of paclitaxel and BEZ235 (NEs-PTX-BEZ235) and to explore the potential key parameters for its clinical translation. This study aims to provide a new therapeutic strategy for colorectal cancer, especially for drug-resistant colorectal cancer. The nanomaterials were prepared by low energy self-emulsification method, and analyzed by Malvern laser particle size analyzer. Cell drug uptake was observed under fluorescence microscope. CCK8, Western blot and flow cytometry were used to compare the anti-cancer effects and mechanisms of different experimental groups on ordinary and drug-resistant colon cancer cells. Human colon cancer primary cells were extracted to verify the anti-tumor effect of drugs. Finally, we found that NEs-PTX-BEZ235 significantly killed colon cancer cells, especially drug-resistant cells, and performed better than Nab-PTX. It may play a synergistic role in reducing drug resistance, inhibiting tumor stemness and inducing apoptosis of colon cancer cells by inhibiting drug resistance proteins.
结直肠癌是最常见的恶性肿瘤之一,其耐药性对人们的健康构成了巨大挑战和严重威胁。在先前的研究中,我们发现紫杉醇与BEZ235联合使用具有协同抗结肠癌作用,尤其是在耐药性结直肠癌中,显示出优异的抗肿瘤效果。因此,本研究旨在研究紫杉醇与BEZ235纳米乳剂(NEs-PTX-BEZ235)的制备,并探索其临床转化的潜在关键参数。本研究旨在为结直肠癌,尤其是耐药性结直肠癌提供一种新的治疗策略。通过低能自乳化法制备纳米材料,并用马尔文激光粒度分析仪进行分析。在荧光显微镜下观察细胞药物摄取情况。采用CCK8、蛋白质免疫印迹法和流式细胞术比较不同实验组对普通和耐药结肠癌细胞的抗癌效果及作用机制。提取人结肠癌原代细胞以验证药物的抗肿瘤作用。最后,我们发现NEs-PTX-BEZ235能显著杀死结肠癌细胞,尤其是耐药细胞,且表现优于纳米白蛋白结合型紫杉醇(Nab-PTX)。它可能通过抑制耐药蛋白在降低耐药性、抑制肿瘤干性和诱导结肠癌细胞凋亡方面发挥协同作用。