Lu Shuya, Gao Jianhui, Jia Huijie, Li Yang, Duan Yongbin, Song Fuyang, Liu Zhiang, Ma Shuai, Wang Mingyong, Zhao Tiesuo, Zhong Jiateng
Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
Department of Pathology, Xinxiang Medical University, Xinxiang, China.
Front Immunol. 2021 Jul 6;12:707991. doi: 10.3389/fimmu.2021.707991. eCollection 2021.
The widespread appearance of drug tolerance and the low efficiency of single treatment have severely affected the survival time of the patients with colorectal cancer. Exploring new treatment options and combined treatment strategies have become the key to improving the prognosis. The combination of immunotherapy and chemotherapy have shown good clinical expectations. Here, we studied the cooperative effects of chloroquine, an anti-malarial drug that is now widely used in anti-tumor research, and RNA interference (RNAi) targeting the immune checkpoint molecule Programmed Death-1 (PD-1) delivered with attenuated . Our results show that chloroquine can not only significantly inhibit the survival of colon cancer cells and induce apoptosis, but also effectively inhibit cell invasion and migration. The results of experiments show that chloroquine can increase the expression of PD-1 in tumor tissues. Combining chloroquine and PD-1 siRNA can further inhibit the growth and metastases of colon cancer and induce apoptosis. The mechanism underlying this phenomenon is the occurrence of chloroquine-induced apoptosis and the effective immune response caused by the attenuated carrying PD-1 siRNA. This study suggests that the combined application of PD-1-based immunotherapy and anti-cancer drugs has become a new expectation for clinical treatment of colorectal cancer.
药物耐受性的广泛出现以及单一治疗的低效性严重影响了结直肠癌患者的生存时间。探索新的治疗选择和联合治疗策略已成为改善预后的关键。免疫疗法与化疗的联合已展现出良好的临床前景。在此，我们研究了氯喹（一种目前广泛应用于抗肿瘤研究的抗疟药物）与通过减毒 递送的靶向免疫检查点分子程序性死亡受体1（PD-1）的RNA干扰（RNAi）的协同作用。我们的结果表明，氯喹不仅能显著抑制结肠癌细胞的存活并诱导凋亡，还能有效抑制细胞侵袭和迁移。实验结果表明，氯喹可增加肿瘤组织中PD-1的表达。氯喹与PD-1 siRNA联合应用可进一步抑制结肠癌的生长和转移并诱导凋亡。这一现象背后的机制是氯喹诱导的凋亡以及由携带PD-1 siRNA的减毒 引发的有效免疫反应。本研究表明，基于PD-1的免疫疗法与抗癌药物的联合应用已成为结直肠癌临床治疗的新期望。
