Department of Laboratory Medicine, The First Affiliated Hospital, Jiamusi University, Jiamusi, 154002, Heilongjiang, China.
Department of Interventional Medicine, The Fifth Hospital, Shijiazhuang, 050000, Hebei, China.
Int Urol Nephrol. 2018 May;50(5):861-868. doi: 10.1007/s11255-018-1818-9. Epub 2018 Mar 9.
We have previously indicated that CXCL3 was upregulated in the tissues of prostate cancer, and exogenous administration of CXCL3 played a predominant role in the tumorigenicity of prostate cancer cells. In the present study, we further explored the role and the underlying mechanism of CXCL3 overexpression in the oncogenic potential of prostate cancer in an autocrine/paracrine fashion.
CXCL3-overexpressing prostate cancer cell line PC-3 and immortalized prostate stromal cell line WPMY-1 were established by gene transfection. CCK-8, transwell assays and growth of tumor xenografts were conducted to characterize the effects of CXCL3 on PC-3 cells' proliferation and migration. Western blotting was conducted to test whether CXCL3 could affect the expression of tumorigenesis-associated genes.
The results showed that CXCL3 overexpression in PC-3 cells and the PC-3 cells treated with the supernatants of CXCL3-transfected WPMY-1 cells stimulated the proliferation and migration of PC-3 cells in vitro and in a nude mouse xenograft model. Western blotting revealed higher levels of p-ERK, Akt and Bcl-2 and lower levels of Bax in the tumor xenografts transplanted with CXCL3-transfected PC-3 cells. Moreover, the tumor xenografts derived from the PC-3 cells treated with supernatants of CXCL3-transfected WPMY-1 cells showed higher expression of ERK, Akt and Bcl-2 and lower expression of Bax.
These findings suggest that CXCL3 autocrine/paracrine pathways are involved in the development of prostate cancer by regulating the expression of the target genes that are related to the progression of malignancies.
我们之前已经表明，CXCL3 在前列腺癌组织中上调，外源性 CXCL3 的给药在前列腺癌细胞的致瘤性中起主要作用。在本研究中，我们进一步探讨了 CXCL3 过表达在前列腺癌细胞自分泌/旁分泌致癌潜能中的作用及其潜在机制。
通过基因转染，建立了 CXCL3 过表达前列腺癌细胞系 PC-3 和永生化前列腺基质细胞系 WPMY-1。通过 CCK-8、Transwell 检测和肿瘤异种移植生长实验，研究了 CXCL3 对 PC-3 细胞增殖和迁移的影响。Western blot 用于检测 CXCL3 是否影响与肿瘤发生相关的基因表达。
结果表明，PC-3 细胞中 CXCL3 的过表达和 CXCL3 转染的 WPMY-1 细胞上清液处理的 PC-3 细胞，在体外和裸鼠异种移植模型中刺激了 PC-3 细胞的增殖和迁移。Western blot 显示，移植 CXCL3 转染的 PC-3 细胞的肿瘤异种移植物中 p-ERK、Akt 和 Bcl-2 的水平升高，Bax 的水平降低。此外，用 CXCL3 转染的 WPMY-1 细胞上清液处理的 PC-3 细胞来源的肿瘤异种移植物中 ERK、Akt 和 Bcl-2 的表达升高，Bax 的表达降低。
这些发现表明，CXCL3 自分泌/旁分泌途径通过调节与恶性肿瘤进展相关的靶基因的表达，参与了前列腺癌的发生。
