AGTR1在结直肠癌发生发展中的调控作用及临床转化研究进展

张 赟政, 刘建 刚*
山东第一医科大学第二附属医院

摘要


结直肠癌（colorectal cancer，CRC）是全球范围内高发的消化系统恶性肿瘤，近年来全球疾病负担逐年攀
升，晚期患者易出现远处转移与术后复发，临床预后普遍欠佳，现有诊疗策略仍存在早期诊断率低、靶向治疗靶点
有限等诸多局限，挖掘新型特异性肿瘤标志物与高效治疗靶点已成为结直肠癌临床转化研究的核心方向。血管紧张
素Ⅱ 1型受体基因（AGTR1）作为肾素-血管紧张素系统（RAS）的关键效应分子，除经典的参与机体血压稳态
调控、水盐代谢平衡等生理功能外，其异常表达与多种实体肿瘤的发生发展及侵袭转移密切相关。现有研究证实，
AGTR1可通过调控肿瘤细胞增殖与凋亡失衡、上皮间质转化进程、肿瘤血管生成及肿瘤微环境重塑等多个关键环
节，参与结直肠癌的恶性进展，兼具预后评估、早期无创诊断及靶向治疗干预的多重潜在应用价值。本文系统梳理
AGTR1的核心生理功能及对癌细胞的影响，全面总结其临床病理意义，深入分析当前领域研究存在的争议与不足，
并对未来基础研究方向与临床转化路径进行展望，旨在为结直肠癌的精准早期诊断、预后分层及新型靶向治疗策略
研发提供系统的理论参考与实践思路。

关键词


AGTR1；结直肠癌；分子标志物；靶向治疗

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参考


[1]Siegel R L, Wagle N S, Cercek A, et al. Colorectal

cancer statistics, 2023[J]. CA Cancer J Clin, 2023, 73(3): 233-

254.

[2]Dzielińska Z, Małek Ł A, Roszczynko M, et al.

Combined renin-angiotensin system gene polymorphisms and

outcomes in coronary artery disease—a preliminary report[J].

Kardiol Pol, 2011, 69(7): 688-695.

[3]Akazawa H, Yano M, Yabumoto C, et al. Angiotensin

II type 1 and type 2 receptor-induced cell signaling[J]. Curr

Pharm Des, 2013, 19(17): 2988-2995.

[4]Nadal J A, Scicli G, Carbini L, Scicli A G.

Angiotensin II stimulates migration of retinal microvascular

pericytes: involvement of TGF-β and PDGF-BB[J]. Am J

Physiol Heart Circ Physiol, 2002, 282(2): H739-H748.

[5]Chua C C, Hamdy R C, Chua B H. Upregulation

of vascular endothelial growth factor by H2O2 in rat heart

endothelial cells[J]. Free Radic Biol Med, 1998, 25(8): 891-897.

[6]Huang J, Guo Y, Lv X, et al. Exploration of effective

biomarkers and infiltrating immune cells in metastatic

colorectal cancer based on bioinformatics analysis[J]. Sci Rep,

2025, 15(1): 33156.[7]Zhou L, Luo Y, Sato S, et al. Role of two types of

angiotensin II receptors in colorectal carcinoma progression[J].

Pathobiology, 2014, 81(4): 169-175.

[8]Carmona F J, Azuara D, Berenguer-Llergo A, et

al. DNA methylation biomarkers for noninvasive diagnosis

of colorectal cancer[J]. Cancer Prev Res (Phila), 2013, 6(7):

656-665.

[9]Lu Y-W, Ding Z-L, Mao R, et al. Early results

of the integrative epigenomic-transcriptomic landscape of

colorectal adenoma and cancer[J]. World J Gastrointest Oncol,

2024, 16(2): 414.

[10]Zhou K, Li G, Pan R, et al. Preclinical evaluation

of AGTR1-Targeting molecular probe for colorectal cancer

imaging in orthotopic and liver metastasis mouse models[J].

Eur J Med Chem, 2024, 271: 116452.

[11]Kedika R, Patel M, Sahdala H N P, et al. Longterm use of angiotensin converting enzyme inhibitors is

associated with decreased incidence of advanced adenomatous

colon polyps[J]. J Clin Gastroenterol, 2011, 45(2).

[12]Engineer D R, Burney B O, Hayes T G, Garcia J

M. Exposure to ACEI/ARB and β-blockers is associated

with improved survival and decreased tumor progression and

hospitalizations in patients with advanced colon cancer[J].

Transl Oncol, 2013, 6(5): 539-545.

[13]Olschewski D N, Hofschröer V, Nielsen N, et al.

The angiotensin II type 1 receptor antagonist losartan affects

NHE1-dependent melanoma cell behavior[J]. Cell Physiol

Biochem, 2018, 45(6): 2560-2576.


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