LDHA inhibitor combined with targeted drugs synergistically inhibit the proliferation of fumarate hydratase-deficient renal cell carcinoma cells
10.3969/j.issn.1009-8291.2023.10.016
- VernacularTitle:LDHA抑制剂与靶向药物联用协同抑制延胡索酸水合酶缺陷型肾癌细胞增殖
- Author:
Yilun HONG
1
;
Jianfeng WANG
1
;
Jin ZHANG
1
Author Information
1. Department of Urology, Renji Hospital, Medical School of Shanghai Jiaotong University, Shanghai 200127, China
- Publication Type:Journal Article
- Keywords:
FH-deficient renal cell carcinoma;
LDHA inhibitor;
targeted drugs;
combined drug treatment;
combination index;
sunitinib;
cabozantinib;
sorafenib;
pazopanib
- From:
Journal of Modern Urology
2023;28(10):900-905
- CountryChina
- Language:Chinese
-
Abstract:
【Objective】 To explore the therapeutic effects of lactate dehydrogenase A (LDHA) inhibitor and targeted drugs on fumarate-hydratase-deficient renal cell carcinoma (FH-d RCC). 【Methods】 RNA-sequencing was used to detect the mRNA expression in FH-d RCC tissues, which was further validated with real-time fluorescence quantitative PCR and immunohistochemistry. Human-derived FH-d RCC cell line UOK262 and murine-derived FH-d RCC cell line FH1-/-CL19 (CL19) were treated with LDHA inhibitor [(R)-GNE-140] and listed kidney cancer targeted drugs (Axitinib, Cabozantinib, Sunitinib, Sorafenib, Pazopanib, Everolimus) respectively, and then treated with LHDA inhibitor in combination with the targeted drugs to observe the alteration of cell proliferation. The combination index (CI) of different dose groups of the combination drugs were analyzed with CompuSyn software to determine the optimal combination regimen. 【Results】 LDHA inhibitor and targeted drugs, including Cabozantinib, Sorafenib and Sunitinib, had a significant inhibitory effect on the proliferation of FH-d RCC cells, and the combination of Cabozantinib and Sorafenib or Pazopanib had a significant anti-tumor effect. 【Conclusion】 LDHA inhibitor combined with targeted drugs can significantly inhibit the growth of FH-d RCC cells, indicating that LDHA may be a potential therapeutic target of FH-d RCC.
