Fang Qiong, Li Zhiying, Xue Ye, Zong Xin, Ma Wenshuang, Xi Guangmin, Zhang Xiao Feng, Li Zuowei
Shandong University of Traditional Chinese Medicine, Jinan, 250000, Shandong, P.R. China.
Health Management Center, People's Hospital of Chengyang, Qingdao, 266109, Shandong, P.R. China.
Anticancer Agents Med Chem. 2023;23(7):807-816. doi: 10.2174/1871520622666220825155125.
Renal cell carcinoma (RCC) is a common malignant tumor of the urinary system with a high recurrence rate and easy metastasis. Current clinical drugs for renal cell carcinoma include immunotherapies and targeted drugs. Axitinib is a clinically targeted drug for treating renal cell carcinoma, which has shortcomings such as unstable efficacy and easy drug resistance. Therefore, this study aims to determine whether embelin can enhance the sensitivity of renal cancer cells to axitinib and explore its regulatory pathways.
The enhancing effect of embelin on axitinib was detected using MTT, crystal violet staining, and annexin VFITC staining in two renal cancer cell lines. Western blot was performed to detect the expression of autophagy-related proteins under different conditions. Bioinformatic tools were used to predict the pathways through which embelin may act on renal cancer cells, and pharmacological methods were used to verify the results.
Embelin enhanced the sensitivity of renal cancer cells to axitinib in the following aspects: enhancing the inhibition of cell proliferation by axitinib, and the induction of cell apoptosis. HIF was a potential pathway for embelin's action. After IOX2 regulated the HIF-1α pathway, the enhancing effect of embelin on axitinib was weakened. Moreover, after PT2977 regulated the HIF-2α pathway, the enhancing effect of embelin on axitinib was weakened.
Embelin enhanced the sensitivity of A498 and 786-O renal cancer cells to axitinib by inhibiting the HIF pathway.
肾细胞癌（RCC）是泌尿系统常见的恶性肿瘤，复发率高且易转移。目前用于肾细胞癌的临床药物包括免疫疗法和靶向药物。阿昔替尼是一种治疗肾细胞癌的临床靶向药物，存在疗效不稳定和易产生耐药性等缺点。因此，本研究旨在确定 embelin 是否能增强肾癌细胞对阿昔替尼的敏感性并探索其调控途径。
在两种肾癌细胞系中，采用 MTT、结晶紫染色和 Annexin V-FITC 染色检测 embelin 对阿昔替尼的增强作用。通过蛋白质免疫印迹法检测不同条件下自噬相关蛋白的表达。利用生物信息学工具预测 embelin 可能作用于肾癌细胞的途径，并采用药理学方法验证结果。
Embelin 在以下方面增强了肾癌细胞对阿昔替尼的敏感性：增强阿昔替尼对细胞增殖的抑制作用以及诱导细胞凋亡。HIF 是 embelin 发挥作用的潜在途径。IOX2 调节 HIF-1α 通路后，embelin 对阿昔替尼的增强作用减弱。此外，PT2977 调节 HIF-2α 通路后，embelin 对阿昔替尼的增强作用减弱。
Embelin 通过抑制 HIF 通路增强了 A498 和 786-O 肾癌细胞对阿昔替尼的敏感性。
