Gu Han, You Wei, Zhou Xiao-Hong, Wang Zhe, Huo Shao-Hu, Nie Xuan, Feng Yu-Bin, You Ye-Zi, Zhan Xiang, Xia Lei
Department of Polymer Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China.
Department of Pediatrics, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P. R. China.
ACS Omega. 2025 Jun 6;10(23):24541-24554. doi: 10.1021/acsomega.5c01251. eCollection 2025 Jun 17.
Breast cancer represents the most common cancer among women worldwide. Triple-negative breast cancer (TNBC), a particularly aggressive, metastatic, and drug-resistant subtype of breast cancer, poses a significant clinical challenge because of its resistance to treatment. The efficacy of commonly employed chemotherapeutic agents, such as paclitaxel, is severely limited. In this study, we identified the chemical compound Halicin, which inhibits the proliferation of various cancers, including TNBC. and experiments demonstrated that Halicin could activate pyruvate kinase M2 from its inactive dimers to active tetramers, changing the metabolism of tumor cells and suppressing tumor growth. Moreover, Halicin disrupted mitochondria and downregulated the antiapoptotic gene Bcl-2 to overcome multidrug resistance. Further experiments revealed that Halicin inhibits the growth of orthotopic breast tumors through intraperitoneal injection. The discovery of Halicin as an anticancer drug holds great promise for the treatment of TNBC.
乳腺癌是全球女性中最常见的癌症。三阴性乳腺癌（TNBC）是一种特别具有侵袭性、转移性和耐药性的乳腺癌亚型，由于其对治疗具有抗性，因此构成了重大的临床挑战。常用化疗药物如紫杉醇的疗效受到严重限制。在本研究中，我们鉴定出化合物Halicin，它能抑制包括TNBC在内的多种癌症的增殖。实验表明，Halicin可将丙酮酸激酶M2从无活性的二聚体激活为有活性的四聚体，改变肿瘤细胞的代谢并抑制肿瘤生长。此外，Halicin破坏线粒体并下调抗凋亡基因Bcl-2以克服多药耐药性。进一步的实验表明，通过腹腔注射，Halicin可抑制原位乳腺肿瘤的生长。Halicin作为一种抗癌药物的发现为TNBC的治疗带来了巨大希望。
