经多肽修饰后的联合化疗药及基因纳米复合物在靶向治疗喉癌干细胞的作用研究

Effect of Peptide Modified Combined Chemotherapy Drugs and Gene Nanocomposites on Targeted Therapy of Laryngeal Cancer Stem Cells

摘要: 目的：靶向杀伤喉癌干细胞已是喉癌治疗的共识。方法：拟用前期已构建的共载PTX与Bmi-1RNAi的壳聚糖–聚乙二醇缓释纳米微粒(mPEG-CS-cRGD/Bmi-1RNAi-PTX)，通过体外和体内试验证实mPEG-CS-cRGD/Bmi-1RNAi-PTX纳米微粒对喉癌Hep-2细胞和喉癌Hep-2细胞所建立的荷瘤裸鼠模型的增殖、凋亡能力的影响及其安全性。比较采用PTX和mPEG-CS-cRGD/Bmi-1RNAi-PTX纳米微粒作用前后CD133和C-myc基因的表达比例差异。结果：比单一应用PTX化疗相比，该纳米微粒联合化疗药物，在可以显著抑制喉癌Hep-2细胞增殖，促进凋亡，而且可以明显抑制移植瘤的生长，并且具有生物安全性。同时，在体外和体内分别可以降低喉癌干细胞的干性标记CD133和C-myc的表达量。结论：cRGD肽、紫杉醇与Bmi-1RNAi可以多重靶向杀伤喉癌干细胞，具有重叠增效机制。

Abstract: Objective: Targeted killing of laryngeal cancer stem cells has become a consensus in the treatment of laryngeal cancer. Methods: The chitosan-polyethylene glycol sustained-release nanoparticles (mPEG-CS-cRGD/Bmi-1RNAi-PTX) co-loaded with PTX and Bmi-1RNAi previously constructed were used. The effects of mPEG-CS-cRGD/Bmi-1RNAi-PTX nanoparticles on the proliferation and apoptosis of laryngeal carcinoma Hep-2 cells and laryngeal carcinoma Hep-2 cells in tumor-bearing nude mice models and their safety were confirmed by in vitro and in vivo experiments. The expression ratios of CD133 and C-myc genes before and after treatment with PTX and mPEG-CS-cRGD/Bmi-1RNAi-PTX nanoparticles were compared. Results: Compared with the single application of PTX chemotherapy, the nanoparticles combined with chemotherapy drugs can significantly inhibit the proliferation of laryngeal carcinoma Hep-2 cells, promote apoptosis, and significantly inhibit the growth of transplanted tumors, with biological safety. At the same time, the expression levels of CD133 and C-myc in laryngeal cancer stem cells can be reduced in vitro and in vivo, respectively. Conclusion: cRGD peptide, paclitaxel and Bmi-1RNAi can kill laryngeal cancer stem cells with multiple targets and have overlapping synergistic mechanism.