甲酰基肽受體1在耐藥膀胱癌中的表達及功能

2018年2月，第四軍醫大學藥學院藥物研究所；氟氮化工國家重點實驗室；西安現代化學研究所 (Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi’an 710032, China；State Key Laboratory of Fluorine & Nitrogen Chemicals, Xi’an 710065, China；Xi’an Modern Chemistry Research Institute, Xi’an 710065, China) Man Zhang老師研究團隊在《Technology in Cancer Research & Treatment》上發表論文：

“Expression and Functions of Formyl Peptide Receptor 1 in Drug-Resistant Bladder Cancer”

“甲酰基肽受體1在耐藥膀胱癌中的表達及功能”

Abstract：

Objective: To explore the correlation of formyl peptide receptor 1 expression with drug resistance and the functions of formyl peptide receptor 1 in drug-resistant bladder cancer.

Methods: Expression of formyl peptide receptor 1 in T24 and T24/DDP cisplatin-resistant bladder cancer cell lines was tested by quantitative real-time Polymerase Chain Reaction and Western blotting. After incubation of T24/DDP with N-formyl-Met-Leu-Phe, the phosphor proteins were tested by Western blot analysis. We characterized the functions of formyl peptide receptor 1 in T24/DDP cells by assessing proliferation, migration, and changes of cell cycles.

Results: Formyl peptide receptor 1 was expressed in both T24 and T24/DDP, and it was overexpressed in T24/DDP compared with T24. Formyl peptide receptor 1 activation promoted the expression of the messenger RNA of resistance-related proteins, such as multidrug resistance-associated protein 1 (MRP1) and lung resistance-related protein (LRP). The expression of 4 signal pathway proteins were upregulated: signal transducer and activator of transcription 3, Janus kinase 2, extracellular regulated protein kinases, and protein kinase B, while the expression of phosphatidylinositol 3-kinase was observed to be downregulated in drug-resistant bladder cancer cells. Formyl peptide receptor 1 activation also improved the expression of phospho-signal transducer and activator of transcription 3 and phospho-extracellular regulated protein kinases 1/2 and promoted the proliferation and migration of T24/DDP cells. In addition, formyl peptide receptor 1 inhibition led to the change in the cell cycle in T24/DDP.

Conclusions: The overexpression of formyl peptide receptor 1 may be related to drug-resistant bladder cancer and promotes the deterioration of drug-resistant bladder cancer.

摘要：

目的:

探討耐藥膀胱癌甲酰基肽受體1表達與耐藥的關系及甲酰基肽受體1的功能。

方法:

采用實時定量聚合酶鏈反應和Western blotting檢測T24和T24/DDP順鉑耐藥膀胱癌細胞株甲酰基肽受體1的表達。將T24/DDP與n -甲酰基met -亮氨酸孵育后，采用Western blot檢測磷酸化蛋白。科研人員通過評估T24/DDP細胞的增殖、遷移和細胞周期變化來表征甲酰基肽受體1在T24/DDP細胞中的功能。

結果:

甲酰基肽受體1在T24和T24/DDP中均有表達，與T24相比，T24/DDP中甲酰基肽受體1過表達。甲酰基肽受體1激活可促進耐藥相關蛋白信使RNA的表達，如多藥耐藥相關蛋白1 (MRP1)和肺耐藥相關蛋白(LRP)。在耐藥膀胱癌細胞中，4種信號通路蛋白表達上調，分別是轉錄信號轉導和激活因子3、Janus激酶2、細胞外調節蛋白激酶和蛋白激酶B，而磷脂酰肌醇3激酶表達下調。激活甲酰基肽受體1還能提高磷酸化信號轉導因子和轉錄激活因子3、磷酸化胞外調節蛋白激酶1/2的表達，促進T24/DDP細胞的增殖和遷移。此外，甲酰基肽受體1的抑制導致T24/DDP細胞周期的改變。

結論:

甲酰基肽受體1的過表達可能與耐藥膀胱癌有關，并促進耐藥膀胱癌的惡化。

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