[1]杨风光,许清江,魏永宝,等.罗格列酮对舒尼替尼耐药肾癌细胞血管生成的影响[J].福建医药杂志,2023,45(03):106-109.
　YANG Fengguang,XU Qingjiang,WEI Yongbao,et al.Effect of peroxisome on angiogenesis in sunitinib-resistant renal carcinoma cells[J].FUJIAN MEDICAL JOURNAL,2023,45(03):106-109.
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罗格列酮对舒尼替尼耐药肾癌细胞血管生成的影响()
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《福建医药杂志》[ISSN:1002-2600/CN:35-1071/R]

卷:
45
期数:
2023年03期
页码:
106-109
栏目:
基础研究
出版日期:
2023-06-15

文章信息/Info

Title:
Effect of peroxisome on angiogenesis in sunitinib-resistant renal carcinoma cells
文章编号:
1002-2600(2023)03-0106-04
作者:
杨风光; 许清江; 魏永宝; 彭俊铭; 张弛; 陈平舟; 阮君山1
福建医科大学省立临床医学院 福建省立医院泌尿外科(福州 350001)
Author(s):
YANG Fengguang;  XU Qingjiang;  WEI Yongbao;  PENG Junming;  ZHANG Chi;  CHEN Pingzhou;  RUAN Junshan
Department of Urology Surgery, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, China
关键词:
肾细胞癌;  过氧化物酶体增殖物激活受体γ;  血管生成;  舒尼替尼耐药
Keywords:
renal cell carcinoma;  peroxisome proliferator activated receptorγ;  angiogenesis;  sunitinib resistance
分类号:
R737.11
文献标志码:
A
摘要:
目的 探讨过氧化物酶体增殖物激活受体γ(PPARγ)配体罗格列酮(RG)对舒尼替尼(SU)耐药的肾癌细胞血管生成的影响及其作用机制。方法 通过浓度梯度培养建立SU耐药的肾癌细胞株(786-O/SR和A498/SR),构建并转染短发夹PPARγ(shPPARγ)慢病毒载体静默PPARγ的表达。细胞生长曲线观察RG对耐药肾癌细胞生长的影响。人脐静脉血管内皮细胞(HUVEC)小管形成实验观察RG对血管生成的作用,以及与PPARγ表达的关系。Western blot检测血管内皮生长因子(VEGF)和蛋白激酶B/信号传导转录激活因子3(AKT/STAT3)通路蛋白表达的变化。结果 RG抑制SU耐药肾癌细胞的生长。30 μmol/L RG抑制786-O/SR和A498/SR细胞生成HUVEC小管的能力,Western blot结果显示VEGF、p-AKT、AKT、p-STAT3、STAT3的表达降低,静默PPARγ可以逆转RG的抑制作用。结论 RG通过激活PPARγ抑制SU耐药肾癌细胞的生长和血管生成,PPARγ配体有可能成为耐药肾癌细胞的治疗药物。
Abstract:
Objective To investigate the effect of PPARγ ligand rosiglitazone(RG)on angiogenesis of sunitinib-resistant renal carcinoma cells and explore its mechanism. Methods Renal cancer cell lines 786-O and A498 were cultured in concentration gradient sunitinib to construct drug resistant cells.Sunitinib resistant cells 786-O/SR and A498/SR were transfected with shPPARγ lentivirus vector to silence PPARγ expression. The effect of rosiglitazone on the growth of drug-resistant cells was detected by cell growth curve. The ability of angiogenesis induced by drug-resistant renal carcinoma cells treated with rosiglitazone were observed by HUVEC tubule formation assay. The expression levels of pathway proteins were detected by Western blot. Results Rosiglitazone inhibited the growth of sunitinib resistant renal carcinoma cells. 30 μmol/L rosiglitazone inhibited the ability of 786-O/SR and A498/SR cells to generate HUVEC tubules. Western blot results showed that the expressions of VEGF, p-AKT, AKT, p-STAT3 and STAT3 were decreased. Silent PPARγ reversed the inhibitory effect of rosiglitazone. Conclusion Rosiglitazone inhibits cell growth and angiogenesis in sunitinib-resistant renal carcinoma cells through activating PPARγ,and may be a potential therapeutic agent for sunitinib-resistance.

参考文献/References:

[1] Small J, Washburn E, Millington K, et al. The addition of abemaciclib to sunitinib induces regression of renal cell carcinoma xenograft tumors[J]. Oncotarget,2017, 8(56):95116-95134.
[2]Morais C. Sunitinib resistance in renal cell carcinoma[J].J Kidney Cancer VHL, 2014,1(1):1-11.
[3]郭鑫,宗欢欢,李杜达,等.PPARγ在肿瘤中的双重作用[J].中国细胞生物学学报, 2021,43(2):460-468.
[4]Kotlinowski J,Jozkowicz A. PPAR Gamma and angiogenesis: endothelial cells perspective[J].J Diabetes Res, 2016,2016:8492353.
[5]Osako Y, Yoshino H, Sakaguchi T, et al. Potential tumor-suppressive role of microRNA-99a-3p in sunitinib-resistant renal cell carcinoma cells through the regulation of RRM2[J]. Int J Oncol,2019,54(5):1759-1770.
[6]Wang Y,Chen S,Sun S, et al. Wogonin induces apoptosis and reverses sunitinib resistance of renal cell carcinoma cells via inhibiting CDK4-RB pathway[J].Front Pharmacol,2020,11:1152.
[7]Kotlinowski J, Jozkowicz A. PPAR gamma and angiogenesis: endothelial cells perspective[J].J Diabetes Res,2016,2016:8492353.
[8]Piatkowska-Chmiel I, Gawrońska-Grzywacz M, Natorska-Chomicka D, et al. Pioglitazone as a modulator of the chemoresistance of renal cell adenocarcinoma to methotrexate[J]. Oncol Rep,2020,43(3):1019-1030.
[9]He M, Xue Y. MicroRNA-148a suppresses proliferation and invasion potential of non-small cell lung carcinomas via regulation of STAT3[J]. Onco Targets Ther,2017,10:1353-1361.
[10]Liu Y, Chen S, Liu J, et al.Telmisartan inhibits oxalate and calcium oxalate crystal-induced epithelial-mesenchymal transformation via PPAR-γ-AKT/STAT3/p38 MAPK-Snail pathway[J]. Life Sci,2020,241:117108.

备注/Memo

备注/Memo:
基金项目:福建省自然科学基金面上项目(2019J01181)
1 福建省立医院中医药分子生物学实验室,通信作者,Email: yangfengguang@fjmu.edu.cn
更新日期/Last Update: 2023-06-15