Chen Hua-Fei, Wu Li-Xin, Li Xiao-Feng, Zhu You-Cai, Wang Wen-Xian, Xu Chun-Wei, Huang Zhang-Zhou, Du Kai-Qi
Department of Thoracic Disease Center, Zhejiang Rongjun Hospital, Jiaxing Zhejiang 314000, China.
Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou Zhejiang 310022, China.
Cell Mol Biol (Noisy-le-grand). 2019 Apr 30;65(4):48-52.
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths. Compound K, an active metabolite of ginsenosides, is reported to exhibit anti-cancer property in various types of human malignancies. The present study investigated the role of compound K on glucose metabolism in NSCLC cells and its underlying mechanism. Our study found that compound K dose-dependently inhibited the cell viability of NSCLC cells. Moreover, administration with compound K decreased glucose uptake and lactate secretion under normoxic and hypoxic conditions. Consistently, the expression of key enzymes (HK II, PDK1 and LDHA) involved in glucose metabolism were inhibited in compound K-treated tumor cells. In addition, compound K inhibited the expression of HIF-1α and its downstream gene GLUT1. On the contrary, overexpression of HIF-1α elevated metabolic reactions and partly attenuated the inhibitory role of compound K on NSCLC cell growth. These results demonstrate that compound K suppresses NSCLC cell growth via HIF-1α mediated metabolic alteration, contributing to novel anticancer therapy by targeting glucose metabolism.
非小细胞肺癌（NSCLC）是癌症相关死亡的主要原因。人参皂苷的活性代谢产物化合物K据报道在各种类型的人类恶性肿瘤中具有抗癌特性。本研究调查了化合物K在NSCLC细胞中对葡萄糖代谢的作用及其潜在机制。我们的研究发现，化合物K剂量依赖性地抑制NSCLC细胞的活力。此外，在常氧和低氧条件下，给予化合物K可降低葡萄糖摄取和乳酸分泌。一致地，化合物K处理的肿瘤细胞中参与葡萄糖代谢的关键酶（HK II、PDK1和LDHA）的表达受到抑制。此外，化合物K抑制HIF-1α及其下游基因GLUT1的表达。相反，HIF-1α的过表达提高了代谢反应，并部分减弱了化合物K对NSCLC细胞生长的抑制作用。这些结果表明，化合物K通过HIF-1α介导的代谢改变抑制NSCLC细胞生长，为通过靶向葡萄糖代谢的新型抗癌治疗做出贡献。
