Angiotensin II enhances the proliferation of Natural Killer/T-cell lymphoma cells via activating PI3K/Akt signaling pathway

Gui-Hua Zhang,Jin-Ge Xu,Fa-An Miao,Yan Zhang

doi:10.1042/bsr20202388

Angiotensin II enhances the proliferation of Natural Killer/T-cell lymphoma cells via activating PI3K/Akt signaling pathway

Gui-Hua Zhang, Jin-Ge Xu + Show 2 more

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https://doi.org/10.1042/bsr20202388

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Abstract

The present study was to determine the roles of Angiotensin (Ang) II in the growth of lymphoma in nude mice and the proliferation and viability of the human Natural Killer/T (NK/T)-cell lymphoma cell line SNK-6, and the activation of downstream signaling pathway. Lymphoma samples and corresponding normal tissues were obtained from lymphoma patients. Proliferation of SNK-6 cells was detected by CCK8 or MTT assay. The levels of Ang II and its receptor Ang II type 1 receptor (AT1R) were higher in lymphoma tissues than those in control tissues. Ang II increased the lymphoma volume and size in nude mice, the proliferation and viability and the proliferating cell nuclear antigen (PCNA) and Ki67 levels of SNK-6 cells. Losartan, an antagonist of AT1R, reduced lymphoma volume and size in nude mice, and the proliferation and viability and the PCNA and Ki67 levels of SNK-6 cells. The levels of phosphorylated phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase B (p-Akt) were increased by Ang II and then reduced by losartan in SNK-6 cells. The proliferation and viability of SNK-6 cells were increased by Ang II, but these increases were inhibited by PI3K inhibitor wortmannin and Akt inhibitor MK2206. The increases of PCNA and Ki67 induced by Ang II were inhibited by wortmannin or MK2206 in SNK-6 cells. These results indicate that Ang II/AT1R is activated in lymphoma, and Ang II promotes the progression of lymphoma in nude mice and the proliferation and viability of SNK-6 cells via activating PI3K/Akt signaling pathway.

Highlights

Arising from extranodal lymphoid tissue or lymph glands, malignant lymphoma shows a growing morbidity globally [1]
Our study found that the expression of Ang II and Ang II type 1 receptor (AT1R) increased in lymphoma tissues
Ang II and AT1R levels increase in gastric cancer tissues compared with healthy tissues [17]

Summary

Introduction

Arising from extranodal lymphoid tissue or lymph glands, malignant lymphoma shows a growing morbidity globally [1]. The renin–angiotensin system (RAS) affects tumor growth and migration by remodeling the tumor microenvironment [3]. Angiotensin (Ang)-(1–7) inhibits cell proliferation, migration and invasion by activating autophagy, which provides a possible treatment option for nasopharyngeal carcinoma (NPC) and recurrent NPC [6]. Expression of Ang II, a crucial biological peptide in the RAS, is closely associated with the development of cancer [7,8]. Ang II produced biological effects via its receptor Ang II type 1 receptor (AT1R) [9,10]. Telmisartan, a specific AT1R blocker, can effectively inhibit the growth of non-small cell lung cancer A549 cell line [11]. Activation of (pro)renin receptor ((P)RR) and AT1R is associated with the pathogenesis of conjunctival extranodal marginal zone B-cell lymphoma (EMZL)

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