PDF(Pubmed)
Abstract：
BACKGROUND: Drug resistance is an important constraint on clinical outcomes in advanced cancers. LAMP2A is a limiting protein in molecular chaperone-mediated autophagy. This study was aimed to explore LAMP2A function in cisplatin (cis-diamminedichloroplatinum, DDP) resistance colorectal cancer (CRC) to seek new ideas for CRC clinical treatment.
METHODS: In this study, LAMP2A expression was analyzed by molecular experimental techniques,such as qRT-PCR and western blot. Then, LAMP2A in cells was interfered by cell transfection experiments. Subsequently, the function of LAMP2A on proliferation, migration, invasion, DDP sensitivity, and autophagy of CRC/DDP cells were further investigated by a series of experiments, such as CCK-8, transwell, and western blot.
RESULTS: We revealed that LAMP2A was clearly augmented in DDP-resistant CRC and was related to poor patient prognosis. Functionally, LAMP2A insertion remarkably CRC/DDP proliferation, migration, invasion ability and DDP resistance by strengthen autophagy. In contrast, LAMP2A knockdown limited the proliferation, migration, and invasion while heightened cellular sensitivity to DDP by restraining autophagy in CRC/DDP cells. Furthermore, LAMP2A silencing was able to curb tumor formation and enhance sensitivity to DDP in vivo.
CONCLUSIONS: In summary, LAMP2A boosted malignant progression and DDP resistance in CRC/DDP cells through mediating autophagy. Clarifying LAMP2A function in DDP resistance is promising to seek cancer therapies biomarkers targeting LAMP2A activity.
METHODS: In this study, LAMP2A expression was analyzed by molecular experimental techniques,such as qRT-PCR and western blot. Then, LAMP2A in cells was interfered by cell transfection experiments. Subsequently, the function of LAMP2A on proliferation, migration, invasion, DDP sensitivity, and autophagy of CRC/DDP cells were further investigated by a series of experiments, such as CCK-8, transwell, and western blot.
RESULTS: We revealed that LAMP2A was clearly augmented in DDP-resistant CRC and was related to poor patient prognosis. Functionally, LAMP2A insertion remarkably CRC/DDP proliferation, migration, invasion ability and DDP resistance by strengthen autophagy. In contrast, LAMP2A knockdown limited the proliferation, migration, and invasion while heightened cellular sensitivity to DDP by restraining autophagy in CRC/DDP cells. Furthermore, LAMP2A silencing was able to curb tumor formation and enhance sensitivity to DDP in vivo.
CONCLUSIONS: In summary, LAMP2A boosted malignant progression and DDP resistance in CRC/DDP cells through mediating autophagy. Clarifying LAMP2A function in DDP resistance is promising to seek cancer therapies biomarkers targeting LAMP2A activity.
摘要：
背景：耐药性是晚期癌症临床结局的重要制约因素。LAMP2A是分子伴侣介导的自噬中的限制性蛋白。本研究旨在探讨LAMP2A在顺铂（顺二氨基二氯铂，DDP)耐药结直肠癌(CRC)寻求CRC临床医治的新思路。
方法：在本研究中，通过分子实验技术分析LAMP2A表达，如qRT-PCR和westernblot。然后，细胞转染实验干扰了细胞中的LAMP2A。随后，LAMP2A对增殖的功能，迁移,入侵,DDP灵敏度,通过一系列实验进一步研究CRC/DDP细胞的自噬,如CCK-8，Transwell，和westernblot.
结果：我们发现LAMP2A在DDP耐药的CRC中明显增强，并且与患者预后不良有关。功能上,LAMP2A插入显着CRC/DDP增殖，迁移,侵袭能力和DDP抗性通过自噬加强。相比之下,LAMP2A敲低限制了增殖，迁移,和侵袭，同时通过抑制CRC/DDP细胞中的自噬提高细胞对DDP的敏感性。此外，LAMP2A沉默能够抑制肿瘤形成并增强体内对DDP的敏感性。
结论：总之，LAMP2A通过介导自噬促进CRC/DDP细胞的恶性进展和DDP抵抗。阐明LAMP2A在DDP抗性中的功能有望寻求靶向LAMP2A活性的癌症治疗生物标志物。
方法：在本研究中，通过分子实验技术分析LAMP2A表达，如qRT-PCR和westernblot。然后，细胞转染实验干扰了细胞中的LAMP2A。随后，LAMP2A对增殖的功能，迁移,入侵,DDP灵敏度,通过一系列实验进一步研究CRC/DDP细胞的自噬,如CCK-8，Transwell，和westernblot.
结果：我们发现LAMP2A在DDP耐药的CRC中明显增强，并且与患者预后不良有关。功能上,LAMP2A插入显着CRC/DDP增殖，迁移,侵袭能力和DDP抗性通过自噬加强。相比之下,LAMP2A敲低限制了增殖，迁移,和侵袭，同时通过抑制CRC/DDP细胞中的自噬提高细胞对DDP的敏感性。此外，LAMP2A沉默能够抑制肿瘤形成并增强体内对DDP的敏感性。
结论：总之，LAMP2A通过介导自噬促进CRC/DDP细胞的恶性进展和DDP抵抗。阐明LAMP2A在DDP抗性中的功能有望寻求靶向LAMP2A活性的癌症治疗生物标志物。
