Jiao Yuan, Peng Xiaobo, Wang Yujie, Hao Zhibin, Chen Ling, Wu Meihong, Zhang Yingyi, Li Jie, Li Wenlin, Zhan Xianbao
Department of Oncology, Changhai Hospital, Naval Medical University, Shanghai 200433, P.R. China.
Department of Cell Biology, Naval Medical University, Shanghai 200433, P.R. China.
Oncol Lett. 2023 Aug 10;26(4):418. doi: 10.3892/ol.2023.14005. eCollection 2023 Oct.
Malignant ascites (MA) is a common manifestation of advanced gastric cancer (GC) with peritoneal metastasis (PM), which usually indicates a poor prognosis. The present study aimed to explore the effects of MA, a unique microenvironment of PM, on the proliferation of cancer cells and investigate the underlying mechanisms. experiments demonstrated that GC cells treated with MA exhibited enhanced proliferation. RNA sequencing indicated that asparagine synthetase () was one of the differentially expressed genes in GC cells following incubation with MAs. Furthermore, the present study suggested that MA induced an upregulation of expression and the stimulatory effect of MA on cancer cell proliferation was alleviated upon downregulation. Activating transcription factor 4 (ATF4), a pivotal transcription factor regulating , was upregulated when cells were treated with MA supernatant. After ATF4 knockdown, the proliferation of MA-treated GC cells and the expression of decreased. In addition, the decline in the proliferation of the ATF4-downregulated AGS GC cell line was rescued by upregulation. The findings indicated that MA could promote the proliferation of GC cells via activation of the ATF4-ASNS axis. Hence, it may be a potential target for treating GC with PM and MA.
恶性腹水（MA）是晚期胃癌（GC）伴腹膜转移（PM）的常见表现，通常提示预后不良。本研究旨在探讨MA（PM的独特微环境）对癌细胞增殖的影响，并研究其潜在机制。实验表明，用MA处理的GC细胞增殖增强。RNA测序表明，天冬酰胺合成酶（ASNS）是与MA孵育后GC细胞中差异表达的基因之一。此外，本研究表明，MA诱导ASNS表达上调，而下调ASNS后，MA对癌细胞增殖的刺激作用减弱。激活转录因子4（ATF4）是调节ASNS的关键转录因子，当用MA上清液处理细胞时，ATF4上调。ATF4敲低后，经MA处理的GC细胞的增殖及ASNS的表达降低。此外，上调ASNS可挽救ATF4下调的AGS GC细胞系增殖的下降。研究结果表明，MA可通过激活ATF4-ASNS轴促进GC细胞的增殖。因此，它可能是治疗伴有PM和MA的GC的潜在靶点。
