Blocking stanniocalcin 2 reduces sunitinib resistance in clear cell renal cell carcinoma

被引：2
作者：
Qin, Zhen-Qian [1 ]
Li, Kong-Dong [2 ]
Chu, He-Zhen [3 ]
Yuan, Xue-Feng [1 ]
Shi, Hai-Feng [2 ]
Gu, Jie [2 ]
Xie, Yi-Min [1 ]
机构：
[1] Jiangsu Univ, Affiliated Hosp, Yixing Hosp, Yixing, Jiangsu, Peoples R China
[2] Jiangsu Univ, Sch Life Sci, Zhenjiang, Jiangsu, Peoples R China
[3] Yangzhou Univ, Affiliated Hosp, Yixing Tradit Chinese Med Hosp, Yixing, Jiangsu, Peoples R China
来源：
NEOPLASMA | 2022年 / 69卷 / 01期
关键词：
stanniocalcin; 2; clear cell renal cell carcinoma; sunitinib; drug resistance; INTERMITTENT SUNITINIB; ELEVATED EXPRESSION; PROGNOSTIC MARKER; STC2; PROLIFERATION; CANCER; GENE; SEQUESTRATION; EVOLUTION; MIGRATION;
D O I：
10.4149/neo_2021_210823N1206
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Stanniocalcin 2 (STC2) has been identified as a prognostic marker in renal cell carcinoma. However, the role of STC2 in renal cell carcinoma is still unclear. In this study, we investigated the relationship between high expression of STC2 and sunitinib resistance in cells and the underlying mechanism. Through GEPIA platform analysis based on TCGA database, it showed that the expression of STC2 in kidney renal clear cell carcinoma (KIRC) was significantly higher than that in the normal population. Real-time quantitative PCR and western blotting detected significantly higher expression levels of STC2 in clear cell renal cell carcinoma (ccRCC) cells than that in normal renal cells. Enzyme-linked immunosorbent assay (ELISA) determined whether there is a high secretion of STC2 in ccRCC cells. The sunitinib resistance could be significantly reduced by STC2 neutralizing antibody but aggravated by the addition of recombinant human STC2 in ccRCC cells. Sunitinib suppressed STC2 expression and secretion, destroyed lysosomal acidic pH, and accumulated in the cells. However, STC2 neutralizing antibody can reduce the accumulation of sunitinib in cells to improve the inhibitory efficiency of sunitinib on cell proliferation. This study suggested STC2 could serve as a potential novel target for the treatment of ccRCC, anti-STC2 antibody might be an option of immunotherapy in the future.
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页码：145 / 154
页数：10
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