Hu Yuzhu, Yu Ting, Liu Xiaoxiao, He Yihong, Deng Lihong, Guo Jiajuan, Hua Yuanqi, Luo Ting, Gao Xiang
Department of Head & Neck and Mammary Oncology and Department of Medical Oncology, Cancer Center, State Key Laboratory of Biotherapy, Laboratory of Molecular Diagnosis of Cancer, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, PR China.
Oncotarget. 2017 Dec 20;9(2):2515-2526. doi: 10.18632/oncotarget.23507. eCollection 2018 Jan 5.
Colorectal cancer is very common worldwide and advanced colorectal cancer exhibited very poor clinical outcome. Oxaliplatin (OXP) is one of the principal chemotherapeutic agents in colorectal cancer treatment presenting impressive anti-tumor ability, limited by adverse effect in clinical practice. Fibrin glue (FG) is a biocompatible formulation made of fibrinogen and thrombin, extensively used in surgery for hemostasis, tissue adhesion and sealing. In this study, FG was innovatively applied as OXP delivery system and results showed enhanced anti-tumor performance in subcutaneous model and abdominal metastasis model of murine colorectal cancer compared with that of OXP used alone. It is revealed that combination of OXP and FG could increase activated CD8 T cells, reduce regulatory T (Treg) cells and increase interferon-γ (IFN-γ). Furthermore, results showed promoted tumor apoptosis, decreased proliferation and inhibited tumor angiogenesis by OXP and FG combination. No obvious systemic toxicity was observed in this study. Finally, our findings provided basis for promising application of OXP and FG combination in colorectal cancer treatment.
结直肠癌在全球范围内非常常见，晚期结直肠癌的临床预后很差。奥沙利铂（OXP）是结直肠癌治疗中的主要化疗药物之一，具有显著的抗肿瘤能力，但在临床实践中受到不良反应的限制。纤维蛋白胶（FG）是一种由纤维蛋白原和凝血酶制成的生物相容性制剂，广泛用于手术中的止血、组织粘连和密封。在本研究中，FG被创新性地用作奥沙利铂的递送系统，结果显示，与单独使用奥沙利铂相比，在小鼠结直肠癌的皮下模型和腹部转移模型中，其抗肿瘤性能增强。结果表明，奥沙利铂与纤维蛋白胶联合使用可增加活化的CD8 T细胞，减少调节性T（Treg）细胞，并增加干扰素-γ（IFN-γ）。此外，结果显示奥沙利铂与纤维蛋白胶联合使用可促进肿瘤细胞凋亡、减少增殖并抑制肿瘤血管生成。本研究未观察到明显的全身毒性。最后，我们的研究结果为奥沙利铂与纤维蛋白胶联合应用于结直肠癌治疗提供了有前景的应用基础。
