Background

Colorectal cancer (CRC) exhibits high risks of morbidity and mortality.

Objective

To investigate the effect of scavenger receptor class A member 5 (SCRAR5) on CRC and its mechanism on modulation of cancer development.

Methods

The SCRAR5 expression in four kinds of CRC cell lines (SW620, SW480, HT29, and HCT116) was measured by quantitative PCR and western blotting, respectively. The effects of SCRAR5 abnormal expression on cell proliferation, apoptosis, and migration were analyzed by CCK-8 assay, EdU assay, colony-forming assay, flow cytometry assay, Transwell assay and wound healing assay, respectively. Meanwhile, the involvements of PI3K/AKT/mTOR pathway with the role of SCRAR5 were investigated by western blotting. Afterwards, the in vivo effects of SCRAR5 abnormal expression on CRC xenograft mice were finally investigated by evaluating tumor volume, apoptosis and Ki67 expression.

Results

SCRAR5 was lowly expressed in CRC cell lines, especially SW480 cells. Up-regulation of SCRAR5 significantly promoted cell apoptosis, reduced cell proliferation and migration in SW480 cells. Notably, SCRAR5 overexpression obviously inhibited the phosphorylation levels of PI3K, AKT, and mTOR. Reversely, SCRAR5 silence exhibited promoting effects on HT29 cells. Consistently, in vivo experiments also revealed that SCRAR5 overexpression remarkably suppressed tumor volume and Ki67 expression, as well as promoted cell apoptosis.

Conclusions

Overall, up-regulating of SCRAR5 obviously inhibited CRC tumor growth in vitro and in vivo, which might be related to PI3K/AKT/mTOR pathway.

中文翻译：

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通过调节 PI3K/AKT/mTOR 通路对结直肠癌中清道夫受体 A 类成员 5 过表达的抑癌作用

背景

结直肠癌 (CRC) 具有很高的发病率和死亡率。

客观的

研究清道夫受体 A 类成员 5 (SCRAR5) 对 CRC 的影响及其调节癌症发展的机制。

方法

分别通过定量PCR和蛋白质印迹测量四种CRC细胞系（SW620、SW480、HT29和HCT116）中SCRAR5的表达。分别采用CCK-8法、EdU法、集落形成法、流式细胞仪法、Transwell法和伤口愈合法分析SCRAR5异常表达对细胞增殖、凋亡和迁移的影响。同时，通过蛋白质印迹研究了PI3K/AKT/mTOR通路参与SCRAR5的作用。随后，通过评估肿瘤体积、细胞凋亡和 Ki67 表达，最终研究了 SCRAR5 异常表达对 CRC 异种移植小鼠的体内影响。

结果

SCRAR5 在 CRC 细胞系中低表达，尤其是 SW480 细胞。在 SW480 细胞中，SCRAR5 的上调显着促进细胞凋亡，减少细胞增殖和迁移。值得注意的是，SCRAR5 过表达明显抑制了 PI3K、AKT 和 mTOR 的磷酸化水平。相反，SCRAR5 沉默对 HT29 细胞表现出促进作用。一致地，体内实验还表明，SCRAR5 过表达显着抑制了肿瘤体积和 Ki67 表达，并促进了细胞凋亡。

结论

总体而言，SCRAR5的上调在体外和体内均明显抑制了CRC肿瘤的生长，这可能与PI3K/AKT/mTOR通路有关。