DST 通过 PI3K/Akt 通路调节结直肠癌的顺铂耐药性

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmacy and Pharmacology Pub Date : 2024-10-17 DOI:10.1093/jpp/rgae104

Jianwei Yu, Xueqiong Deng, Xueqin Lin, Li Xie, Sisi Guo, Xiaoliang Lin, Dong Lin

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引用次数: 0

摘要

研究目的Dystonin（DST）是一种潜在的肿瘤抑制基因，在调节癌细胞增殖和抗化疗方面发挥着至关重要的作用。然而，DST 在结直肠癌（CRC）中的具体作用尚未得到深入研究，本研究旨在阐明其在调节 CRC 的顺铂（DDP）耐药性中的分子作用：方法：分析DST在CRC肿瘤、DDP耐药CRC组织、癌旁组织和正常组织中的表达。在晚期 CRC 和 DDP 耐药细胞系中进行慢病毒过表达和 shRNA 敲除，以评估细胞活力、凋亡、侵袭、迁移、增殖和血管生成。异种移植小鼠模型研究了 DST 对 CRC 肿瘤生长和体内 DDP 抗性的影响：结果：与癌旁组织和正常组织相比，DST在CRC肿瘤和对DDP耐药的CRC组织中的表达明显降低（P < .001）。上调 DST 可抑制 CRC 和 DDP 耐药细胞的活力、增殖、侵袭和迁移，同时促进细胞凋亡。DST 的过表达还能减少血管生成，减弱 DDP 诱导的 CRC 细胞毒性。从机理上讲，DST的上调通过PI3K/Akt信号通路抑制了CRC细胞对DDP的耐药性。上调 DST 可降低 CRC 肿瘤的生长并减轻体内的 DDP 抗性：结论：DST 在限制 CRC 进展和克服 DDP 抗性方面发挥着关键作用，这表明 DST 有可能成为 CRC 的靶向疗法。

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DST regulates cisplatin resistance in colorectal cancer via PI3K/Akt pathway.

Objectives: Dystonin (DST), a potential tumor suppressor gene, plays a crucial role in regulating cancer cell proliferation and resistance to chemotherapy. However, DST's specific role in colorectal cancer (CRC) has not been thoroughly investigated, and this study aims to elucidate its molecular role in modulating cisplatin (DDP) resistance in CRC.

Methods: DST expression was analyzed in CRC tumors, DDP-resistant CRC tissues, paracancer tissues, and normal tissues. Lentiviral overexpression and shRNA knockdown were conducted in advanced CRC and DDP-resistant cell lines to assess cell viability, apoptosis, invasion, migration, proliferation, and angiogenesis. Xenograft mouse models studied DST's impact on CRC tumor growth and DDP resistance in vivo.

Results: DST expression was significantly reduced in CRC tumor and DDP-resistant CRC tissues compared to paracancer and normal tissues (P < .001). Upregulating DST inhibited CRC and DDP-resistant cell viability, proliferation, invasion, and migration while promoting apoptosis. DST overexpression also reduced angiogenesis and attenuated DDP-induced cytotoxicity in CRC cells. Mechanistically, DST upregulation suppressed DDP resistance in CRC cells via the PI3K/Akt signaling pathway. DST upregulation reduced CRC tumor growth and mitigated DDP resistance, in vivo.

Conclusion: DST plays a crucial role in limiting CRC progression and overcoming DDP resistance, suggesting potential for targeted CRC therapies.

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来源期刊

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.