RGS1 serves as an antitumor target to inhibit proliferation of NICN87-DR cells and tumor growth in the gastric cancer mouse model.

Zhixiong Chen, Banglun Liu, Shouru Zhang, Lihui Chen, Yuyu Lv, Hao Sun
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Abstract

Gastric cancer is becoming the 4th leading cause of cancer-associated death worldwide. The purpose of this study was to investigate the role of RGS1 in gastric cancer in vitro and in vivo. Proliferation, migration, invasion, and colony formation of NCIN87 cells and drug-resistant NCIN87 cells (NCIN87-DR) were determined. Cell apoptosis and cell cycle were examined using a flow cytometry assay. RGS1 gene knock-down vector (pLVshshRGS1) and Xenograft tumor mouse model was generated. RGS1 and epithelial-mesenchymal transition (EMT) associated markers, including E-cadherin (E-cad), N-cadherin (N-cad), Slug, and Vimentin were detected using a western blotting assay. Tumor size of Xenograft tumor mouse was measured and Ki67 expression was detected using the immunohistochemical assay. NCIN87-DR cells demonstrated significantly lower proliferation, migration, and invasion compared to those of NCIN87 cells (p < 0.05). NCIN87-DR cells showed obvious early apoptosis and displayed obvious alterations for the cell cycle. NCIN87-DR cells exhibited predominantly higher RGS1 expression than that in NCIN87 cells (p < 0.01). E-cad expression was markedly decreased (p < 0.01) and N-cad (p < 0.05), Slug (p < 0.01), Vimentin (p < 0.05) expressions were significantly increased in NCIN87-DR cells than those in NCIN87 cells. RGS1 gene silence remarkably reduced NCIN87-DR proliferation compared to that in NCIN87-DR cells without treatment (p < 0.01). RGS1 gene-silenced NCIN87-DR cell immunization predominantly inhibited tumor growth in Xenograft tumor mouse than that without RGS1 silence (p < 0.05). RGS1 gene-silenced NCIN87-DR cell immunization significantly downregulated Ki67 expression in tumor tissues compared with that without RGS1 silence. In conclusion, RGS1 gene silence reduced the proliferation of NCIN87-DR cells in vitro and inhibited tumor growth in vivo. Therefore, RGS1 served as an antitumor target for the gastric cancer treatment.

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RGS1作为抗肿瘤靶点,在胃癌小鼠模型中抑制NICN87-DR细胞增殖和肿瘤生长。
胃癌正在成为全球第四大癌症相关死亡原因。本研究旨在探讨RGS1在体外和体内胃癌中的作用。检测NCIN87细胞和耐药NCIN87细胞(NCIN87- dr)的增殖、迁移、侵袭和集落形成。流式细胞术检测细胞凋亡和细胞周期。构建RGS1基因敲除载体(pLVshshRGS1)和异种移植瘤小鼠模型。采用western blotting法检测RGS1和上皮间质转化(EMT)相关标志物,包括E-cadherin (E-cad)、N-cadherin (N-cad)、Slug和Vimentin。采用免疫组化法检测异种移植瘤小鼠的肿瘤大小和Ki67的表达。与NCIN87细胞相比,NCIN87- dr细胞的增殖、迁移和侵袭能力明显降低(p < 0.05)。NCIN87-DR细胞早期凋亡明显,细胞周期变化明显。NCIN87- dr细胞RGS1表达明显高于NCIN87细胞(p < 0.01)。NCIN87- dr细胞中E-cad表达量显著低于NCIN87细胞(p < 0.01), N-cad (p < 0.05)、Slug (p < 0.01)、Vimentin (p < 0.05)表达量显著高于NCIN87细胞。RGS1基因沉默与未处理NCIN87-DR细胞相比,显著降低了NCIN87-DR细胞的增殖(p < 0.01)。RGS1基因沉默的NCIN87-DR细胞免疫能显著抑制异种移植瘤小鼠的肿瘤生长(p < 0.05)。与RGS1基因沉默的NCIN87-DR细胞免疫相比,RGS1基因沉默的NCIN87-DR细胞免疫可显著下调Ki67在肿瘤组织中的表达。综上所述,RGS1基因沉默在体外抑制NCIN87-DR细胞的增殖,在体内抑制肿瘤生长。因此,RGS1可作为胃癌治疗的抗肿瘤靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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