Dong Chao, Chen Yin, Ma Jing, Yang Runxiang, Li Hongjian, Liu Rong, You Dingyun, Luo Chunxiang, Li Heng, Yang Siyuan, Ke Kunbin, Lin Marie Chia-Mi, Chen Ceshi
Department of The Second Medical Oncology, The 3rd Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital Kunming, China.
Department of Urology, Changhai Hospital, Navy Medical University (Second Military Medical University) Shanghai, China.
Am J Cancer Res. 2020 Jan 1;10(1):263-274. eCollection 2020.
Activation of the phosphoinositide 3 kinase (PI3K)/AKT pathway is frequently implicated in resistance to anticancer therapies. PI3K inhibitors can restore sensitivity to standard breast cancer therapies, including endocrine therapy, HER2-targeted agents, and chemotherapy. Our previous research showed that econazole, a novel PI3Ka inhibitor, inhibits the PI3K/AKT pathway and induces apoptosis in lung cancer cells. In this study, econazole showed significant cytotoxic activity against Adriamycin-resistant breast cancer cells and . Additionally, econazole significantly sensitized MDA-MB-231 and MCF-7 cells to Adriamycin via inhibiting the PI3K/AKT pathway. Overexpression of constitutively active AKT1 abolished the function of econazole. The combination of econazole and Adriamycin exerted synergistic inhibitory effects in breast cancer cells and . Taken together, the PI3K inhibitor econazole could effectively overcome Adriamycin resistance and showed synergistic effects with chemotherapy on breast cancer.
磷酸肌醇3激酶（PI3K）/AKT信号通路的激活常常与抗癌治疗耐药相关。PI3K抑制剂能够恢复对包括内分泌治疗、HER2靶向药物和化疗在内的标准乳腺癌治疗的敏感性。我们之前的研究表明，新型PI3Ka抑制剂益康唑可抑制PI3K/AKT信号通路并诱导肺癌细胞凋亡。在本研究中，益康唑对阿霉素耐药的乳腺癌细胞显示出显著的细胞毒活性。此外，益康唑通过抑制PI3K/AKT信号通路使MDA-MB-231和MCF-7细胞对阿霉素显著敏感。组成型活性AKT1的过表达消除了益康唑的作用。益康唑与阿霉素联合使用对乳腺癌细胞发挥协同抑制作用。综上所述，PI3K抑制剂益康唑可有效克服阿霉素耐药，并与化疗对乳腺癌显示出协同作用。
