Chen Sijun, Wu Feijing, Zhang Jiaxuan, Zhu Jianwei, Zhou Xiaorong, Zhi Xiaofei
Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
Department of General Surgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314000, Zhejiang, China.
J Oncol. 2023 Feb 3;2023:6413796. doi: 10.1155/2023/6413796. eCollection 2023.
Gastrointestinal stromal tumor (GIST) originates from a pacemaker cell, the Cajal cell. However, little is known about the cancer neuroscience in GIST. In this study, we aimed to elucidate the clinical and biological roles of adrenoceptor beta 2 (ADRB2) in GIST.
Immunohistochemistry was used to evaluate the expression of ADRB2 in GIST tissues. The biological effects of ADRB2 on GIST cell proliferation, migration, invasion, and apoptosis were explored using Cell Counting Kit -8, plate colony formation assay, transwell invasion assay, and flow cytometry. We also explored the growth and metastasis of xenograft tumors in nude mice. Western blotting was used to quantify protein expression and phosphorylation.
ADRB2 is generally highly expressed in GIST. High ADRB2 expression was significantly associated with risk level, tumor size, mitotic count, and metastasis. Overexpression of ADRB2 promoted GIST cell proliferation, migration, invasion, and apoptosis, while silencing ADRB2 expression showed the opposite effects. Furthermore, we found that silencing endogenous ADRB2 inhibited GIST progression and metastasis in nude mice. ADRB2-induced ETV1 upregulation enhanced the activation of c-KIT.
ADRB2 plays an important role in the proliferation and metastasis of GIST and is expected to be a potential target for the treatment of GIST.
胃肠道间质瘤(GIST)起源于一种起搏细胞,即 Cajal 细胞。然而,关于 GIST 中的癌症神经科学知之甚少。在本研究中,我们旨在阐明肾上腺素能受体β2(ADRB2)在 GIST 中的临床和生物学作用。
采用免疫组织化学法评估 ADRB2 在 GIST 组织中的表达。使用细胞计数试剂盒 -8、平板集落形成试验、Transwell 侵袭试验和流式细胞术探究 ADRB2 对 GIST 细胞增殖、迁移、侵袭和凋亡的生物学效应。我们还探究了裸鼠体内异种移植瘤的生长和转移情况。采用蛋白质印迹法对蛋白质表达和磷酸化进行定量分析。
ADRB2 在 GIST 中通常高表达。ADRB2 高表达与风险水平、肿瘤大小、有丝分裂计数和转移显著相关。ADRB2 的过表达促进了 GIST 细胞的增殖、迁移、侵袭和凋亡,而沉默 ADRB2 表达则显示出相反的效果。此外,我们发现沉默内源性 ADRB2 可抑制裸鼠体内 GIST 的进展和转移。ADRB2 诱导的 ETV1 上调增强了 c-KIT 的激活。
ADRB2 在 GIST 的增殖和转移中起重要作用,有望成为治疗 GIST 的潜在靶点。