Peng Zi-Mei, Xiong Jin-Yong, Deng Feng-Yi, Wang Xing, Wang Tao, Yang Chun-Xi, Chen Yan-Ru, Han Xiao-Jian, Zhang Zhen
Institute of Clinical Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China.
Centre for Medical Research and Translation, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, China.
Cancer Gene Ther. 2025 Jun 22. doi: 10.1038/s41417-025-00929-1.
Chemoresistance and metastasis remain significant challenges in cancer therapy, resulting in treatment failures for cancer patients. Therefore, there is a need to investigate the mechanisms underlying cancer chemoresistance and metastasis, identify novel drug targets, and develop innovative antitumor medications. In this study, we have shown that the ubiquitin conjugating enzyme UBE2N plays a crucial role in promoting chemoresistance and metastasis in lung adenocarcinoma (LUAD) both in vitro and in vivo. Significantly, our study revealed that the natural compound wilforine functions as a potential inhibitor of UBE2N, effectively reversing resistance to cisplatin (CDDP) and inhibiting metastasis of LUAD both in vitro and in vivo. Our findings collectively suggest that UBE2N may have a pivotal role in the development of chemoresistance and metastasis in LUAD, providing a foundation for potential therapeutic strategies in the management of advanced cancer.
化疗耐药性和转移仍然是癌症治疗中的重大挑战，导致癌症患者治疗失败。因此，有必要研究癌症化疗耐药性和转移的潜在机制，确定新的药物靶点，并开发创新的抗肿瘤药物。在本研究中，我们已经表明泛素结合酶UBE2N在体外和体内促进肺腺癌（LUAD）的化疗耐药性和转移中起着关键作用。重要的是，我们的研究表明天然化合物雷公藤灵碱作为UBE2N的潜在抑制剂，在体外和体内均能有效逆转对顺铂（CDDP）的耐药性并抑制LUAD的转移。我们的研究结果共同表明，UBE2N可能在LUAD的化疗耐药性和转移发展中起关键作用，为晚期癌症管理中的潜在治疗策略提供了基础。
