Heo Jinju, Jo Yunhui, Yoon Myonggeun
Department of Bio-Medical Engineering, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul, 02841, Korea.
Institute of Global Health Technology (IGHT), Korea University, Seoul, Republic of Korea.
Clin Transl Oncol. 2025 Mar 24. doi: 10.1007/s12094-025-03898-x.
This study aimed to evaluate the therapeutic potential of combining cabozantinib, electric fields (EFs; also called Tumor Treating Fields [TTFields]), and radiation in the treatment of metastatic renal cell carcinoma (RCC), focusing on overcoming resistance to conventional monotherapeutic regimens.
Human renal cancer cell lines (A498, Caki-1) were treated with cabozantinib (10 µM) for at least 6 h, TTFields (200 kHz, 0.8 V/cm) for 24 h, and radiation (3 Gy), both individually and in combination. Cellular responses, including proliferation, apoptosis, and metastatic potential, were analyzed by flow cytometry and Transwell assays.
The combination of cabozantinib, TTFields, and radiation exhibited synergistic effects, significantly reducing cell proliferation, enhancing apoptosis, and suppressing metastatic capacity compared with individual treatments. Triple therapy resulted in marked inhibition of metastasis-related markers and changes in apoptotic profiles compared with the control group.
This multimodal therapy demonstrated superior efficacy in reducing the metastatic potential and prolonging the survival of RCC cells, offering a promising approach to overcoming treatment resistance in patients with metastatic RCC.
本研究旨在评估卡博替尼、电场（EFs；也称为肿瘤治疗电场[TTFields]）和放疗联合应用于转移性肾细胞癌（RCC）治疗的潜力，重点在于克服对传统单一治疗方案的耐药性。
人肾癌细胞系（A498、Caki-1）分别用卡博替尼（10 μM）处理至少6小时、TTFields（200 kHz，0.8 V/cm）处理24小时和放疗（3 Gy）处理，包括单独处理和联合处理。通过流式细胞术和Transwell实验分析细胞反应，包括增殖、凋亡和转移潜能。
与单独治疗相比，卡博替尼、TTFields和放疗联合应用具有协同效应，显著降低细胞增殖、增强凋亡并抑制转移能力。与对照组相比，三联疗法显著抑制转移相关标志物并改变凋亡特征。
这种多模式疗法在降低RCC细胞转移潜能和延长其生存期方面显示出卓越疗效，为克服转移性RCC患者的治疗耐药性提供了一种有前景的方法。
