Resveratrol liposomes reverse sorafenib resistance in renal cell carcinoma models by modulating PI3K-AKT-mTOR and VHL-HIF signaling pathways

被引:2
作者
Wang, Ligang [1 ]
Wang, Ying [2 ]
Xie, Qiqi [3 ]
Xu, Songcheng [1 ]
Yang, Chen [1 ]
Liu, Fei [4 ]
Liu, Yang [1 ]
Wang, Fuwei [5 ,6 ]
Chen, Weinan [1 ]
Li, Jianchun [1 ]
Sun, Litao [1 ]
机构
[1] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Canc Ctr,Dept Ultrasound Med, 158 Shangtang Rd, Hangzhou, Zhejiang, Peoples R China
[2] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Hlth Management Ctr,Hlth Promot Ctr, Hangzhou, Zhejiang, Peoples R China
[3] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Heart Ctr,Dept Cardiovasc Med, Hangzhou, Zhejiang, Peoples R China
[4] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Rehabil & Sports Med Res Inst Zhejiang Prov, Ctr Rehabil Med,Dept Rehabil Med,Affiliated People, Hangzhou, Zhejiang, Peoples R China
[5] Zhejiang Prov Peoples Hosp, Dept Oncol, Hangzhou 310014, Zhejiang, Peoples R China
[6] Zhejiang Prov Peoples Hosp, Canc Biotherapy Ctr, Hangzhou 310014, Zhejiang, Peoples R China
关键词
Resveratrol liposomes; Sorafenib; Resistance; Combination; Renal cell carcinoma; PI3K-AKT-mTOR; VHL-HIF; Signaling pathway; HEPATOCELLULAR-CARCINOMA; RAF/MEK/ERK PATHWAY; INHIBITION; TARGETS;
D O I
10.1016/j.ijpx.2024.100280
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
RCC is a malignant tumor arising from the urothelium of renal parenchyma that remains challenging to be treated. In this study, we assessed the anti-tumor effects of Resveratrol liposomes (RES-lips) combined with sorafenib on renal cell carcinoma (RCC) and explored the potential mechanisms underlying the improvement of sorafenib resistance models. Tumor growth and survival following treatment with sorafenib alone or in combination with RES-lips was evaluated in a RCC xenograft mouse model. Flow cytometry results demonstrated that the combination of RES-lips and sorafenib significantly enhanced the G1/S phase arrest of sorafenib-resistant cells. When compared with the PBS or monotherapy groups, treatment with RES-lips combined with sorafenib exhibited significant inhibition of tumor growth in the RCC xenograft mouse model with tumor growth inhibition (TGI) rates and complete remission (CR) rates of 90.1 % and 50 %, respectively. Concersely, the maximum TGI rate was 53.6 % in the RES-lips monoherapy group and 29.2 % and in the sorafenib monotherapy group, and no animals achieved CR. Additionally, the current combination therapy promoted the proliferation of unactivated splenic lymphocytes and the proliferation of soybean protein A- and lipopolysaccharide-stimulated lymphocytes compared with PBS or monotherapy treatments. Further western blotting analysis suggested that RES-lips may enhance the resistance of RCC to sorafenib by inhibiting PI3K-AKT-mTOR and VHL-HIF signaling pathways, ultimately augmenting the tumor growth inhibition effect of the combination therapy. RES-lips may improve the sorafenib resistance in RCC, and the underlying mechanism may be related to the regulation of PI3K-AKT-mTOR and VHL-HIF signaling pathways.
引用
收藏
页数:11
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