MTI-31 与 RAD001 联合通过激活自噬抑制肾癌的肿瘤生长和侵袭。
Combining MTI-31 with RAD001 inhibits tumor growth and invasion of kidney cancer by activating autophagy.
发表日期:2023 Nov 07
作者:
Wenye Zhang, Chen Yang, Lujia Zou, Yiwen Zang, Jimeng Hu, Yun Hu, Chenyang Xu, Rongzong Liu, Hao Wang, Zuquan Xiong
来源:
Cellular & Molecular Immunology
摘要:
大多数时候,诊断为肾癌的患者应该接受全身治疗,因为耐药性是该疾病治疗中的一个具有挑战性的问题。 mTOR 抑制剂 RAD001(依维莫司)和 MTI-31 可以抑制癌症的进展。文献表明,这些 mTOR 抑制剂具有刺激自噬的潜力。这种降解途径提高了接受抗癌治疗的癌细胞的存活率。在本研究中,进行了 CCK8、集落形成测定和乙炔基脱氧尿苷 (EdU) 分析来检测细胞增殖。此外,还进行了 Transwell 测定以进行细胞迁移分析。除此之外,研究人员还进行了流式细胞术来识别正在发生凋亡的细胞。在体内,进行实验来测量肿瘤的生长和转移。在这项研究中,通过MTI-31和RAD001的组合提供的治疗显着抑制了肾癌细胞的增殖和肿瘤生长。此外,肾癌细胞对邻近细胞的迁移和侵袭显着减少。机制研究的结果推断,MTI-31 和 RAD001 的组合增加了 LC3 水平,进而转化为自噬的激活。总之,MTI-31 和 RAD001 的组合通过促进自噬提高了 RAD001 在体内产生的抗癌作用。© 2023。作者获得波兰科学院植物遗传学研究所的独家许可。
At most of the times, patients who are diagnosed with kidney cancer should be provided with systemic treatment as drug resistance is a challenging issue in the treatment of this disease. The progression of the cancer can be inhibited with the help of mTOR inhibitors namely RAD001 (everolimus) and MTI-31. In literature, it has been revealed that these mTOR inhibitors have the potential to stimulate autophagy. This degradation pathway boosts the survival rate of the cancerous cells that are subjected to anti-cancer therapy. In this study, CCK8, colony formation assays, and ethynyl deoxyuridine (EdU) analysis were conducted to detect cell proliferation. Furthermore, Transwell assays were also conducted for cell migration analysis. In addition to these, the researchers also performed the flow cytometry process to identify the cells that are undergoing apoptosis. In vivo, experiments were conducted to measure the growth of tumors and metastasis. In this study, the treatment provided through a combination of MTI-31 and RAD001 significantly inhibited the kidney cancer cells' proliferation and tumor growth. Furthermore, there was a notable reduction in the migration and invasion of kidney cancer cells upon the neighboring cells. The outcomes from the mechanistic studies infer that the combination of MTI-31 and RAD001 increases the LC3 levels, which in turn translates into the activation of autophagy. To conclude, the combination of MTI-31 and RAD001 improves the anti-cancerous impact produced by RAD001 in vivo through the promotion of autophagy.© 2023. The Author(s), under exclusive licence to Institute of Plant Genetics Polish Academy of Sciences.