Establishment of an experimental therapy for aggressive renal cell carcinoma by knock-down of SPARC gene expression.

肾细胞癌(RCC)是指具有不同病理和分子生物学异常的异质性肿瘤亚型。虽然大多数肾细胞癌在早期发现后手术治疗成功，但一些组织学类型，如肉瘤样癌和集合管癌是侵袭性的，对辅助治疗耐药。本研究旨在通过siRNA下调SPARC基因的表达，为侵袭性肾癌的治疗提供一种新的途径。为了抑制SPARC基因的表达，我们合成了21个碱基对的dsRNAs，并用脂质体法将其导入肾癌细胞系。只有一个细胞株的SPARC表达下降，而其他三个细胞株(ACHN、CAM-1、YCR)均未显示出SPARC的表达。DRY没有表现出生长抑制、琼脂平板集落形成和裸鼠致瘤性，SPARC作为肾癌治疗的分子靶点的价值值得重新评估。未来，我们应该以HIF-VEGF-SAPRC通路中的其他分子为靶点进行研究。

Renal cell carcinoma (RCC) involves heterogenous subtypes of tumors with different pathology and molecular biological abnormalities. Although most of RCCs is successfully treated with surgery after detection in the early stages, several histological types, i.e. sarcomatoid and collecting duct carcinoma are aggressive and resistant to adjuvant treatment. This research aimed to establish a novel therapy for aggressive RCCs by knock down the SPARC gene expression by siRNA. For suppress the SPARC gene expression, we synthesized 21base pair dsRNAs and introduced them into RCC cell lines by the Lipofectamine method. Only one cell line DRY showed decreased expression of SPARC, but not other three lines (ACHN, CAM-1, YCR) .DRY failed to show growth suppression, colony formation on agar plates or tumorigenicity in nude mice.The value of SPARC as the molecular target of RCC treatment should be carefully reevaluated. In future, we should examine the other molecules in the HIF-VEGF-SAPRC pathway as the target.