Mechanism of small molecule inhibitors targeting CD147 on abnormal proliferation of triple negative breast cancer by mediating reprogramming of glucose metabolism
FU Zhiguang1, LI Hongqi1, YAN Maohui1, LIU Chen1, FAN Chongxi2
1. Department of Radiation Therapy, Characteristics Medical Center of Chinese PLA Air Force, Beijing 100042, China; 2. Department of Gastroenterology, Characteristics Medical Center of Chinese PLA Air Force, Beijing 100042, China
Abstract：Objective To investigate the effect and mechanism of small molecule inhibitors targeting CD147 on the abnormal proliferation of triple negative breast cancer (TNBC) by mediating reprogramming of glucose metabolism. Methods AC-73,small molecule inhibitor torgeting CD147 was chemically modified to obtain the candidate modification inhibitors HA-08 (a small molecule inhibitor targeting CD147). Biochemical tests related with glucose metabolism were used to evaluate whether HA-08 was involved in the reprogramming process of glucose metabolism in TNBC . The blocking effect of HA-08 on the abnormal proliferation of TNBC cells was verified by WST-1 cell proliferation assay. Bioinformatics analysis combined with molecular biological verification was used to elucidate the molecular mechanism of HA-08 blocking the interaction between CD147 and its ligands. Results Eight candidate compounds were modified preliminarily, and HA-08 was selected as the object of this study through biological verification. Glycolytic experiments showed that HA-08 could up-regulate the extracellular pH level, inhibit the release of TNBC lactic acid and the activity of lactate dehydrogenase (LDH), and reduce the glucose uptake of TNBC cells. Proliferation inhibition assay showed that HA-08 reduced the abnormal proliferation of TNBC cells in a time-concentration dependent manner. Co-ip assay showed that the molecular mechanism of HA-08 was closely related with its blocking of the interaction between CD147 and MCT1. Conclusions HA-08 can inhibit the abnormal proliferation of TNBC cells by blocking the interaction of CD147-MCT1, thereby mediating the reprogramming of TNBC glucose metabolism.
付之光, 李宏奇, 闫茂慧, 刘晨, 范崇熙. 靶向CD147小分子抑制剂通过介导糖代谢重编程干预三阴性乳腺癌异常增殖机制[J]. 武警医学, 2023, 34(4): 281-286.
FU Zhiguang, LI Hongqi, YAN Maohui, LIU Chen, FAN Chongxi. Mechanism of small molecule inhibitors targeting CD147 on abnormal proliferation of triple negative breast cancer by mediating reprogramming of glucose metabolism. Med. J. Chin. Peop. Armed Poli. Forc., 2023, 34(4): 281-286.
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2023, Vol. 34 
