RCC 是一种起源于肾实质尿路上皮的恶性肿瘤，治疗仍然具有挑战性。在本研究中，我们评估了白藜芦醇脂质体（RES-lips）联合索拉非尼对肾细胞癌（RCC）的抗肿瘤作用，并探讨了改善索拉非尼耐药模型的潜在机制。在 RCC 异种移植小鼠模型中评估了单独使用索拉非尼或与 RES-lips 联合治疗后的肿瘤生长和存活率。流式细胞术结果表明，RES-lips和索拉非尼的组合显着增强了索拉非尼耐药细胞的G1/S期阻滞。与 PBS 或单一治疗组相比，RES-lips 联合索拉非尼治疗在 RCC 异种移植小鼠模型中表现出显着的肿瘤生长抑制作用，肿瘤生长抑制 (TGI) 率和完全缓解 (CR) 率分别为 90.1% 和 50% ， 分别。相反，RES-lips 单一疗法组的最大 TGI 率为 53.6%，索拉非尼单一疗法组为 29.2%，并且没有动物达到 CR。此外，与 PBS 或单一疗法相比，当前的联合疗法促进了未激活的脾淋巴细胞的增殖以及大豆蛋白 A 和脂多糖刺激的淋巴细胞的增殖。进一步的蛋白质印迹分析表明，RES-lips可能通过抑制PI3K-AKT-mTOR和VHL-HIF信号通路增强RCC对索拉非尼的耐药性，最终增强联合治疗的肿瘤生长抑制效果。 RES-lips可改善RCC对索拉非尼的耐药，其机制可能与PI3K-AKT-mTOR和VHL-HIF信号通路的调节有关。© 2024 The Authors。

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.© 2024 The Authors.