Tumor cells, especially drug-resistant cells, predominately support growth by glycolysis even under the condition of adequate
oxygen, which is known as the Warburg effect.
Glucose metabolism reprogramming is one of the main factors causing
tumor resistance. Previous studies on
Shenmai injection (SMI), a Chinese herbal medicine, have shown enhanced efficacy in the treatment of
tumors in combination with
chemotherapy drugs, but the mechanism is not clear. In this study, we investigated the effect of SMI combined with
cisplatin on
cisplatin-resistant
lung adenocarcinoma A549/DDP cells. Our results showed that
cisplatin-resistant A549/DDP cells exhibited increased
glucose consumption,
lactate production, and expression levels of key glycolytic
enzymes, including
hexokinase 2 (HK2),
pyruvate kinase M1/2 (PKM1/2),
pyruvate kinase M2 (PKM2),
glucose transporter 1 (GLUT1), and
lactate dehydrogenase A (LDHA), compared with
cisplatin-sensitive A549 cells. SMI combined with
cisplatin in A549/DDP cells, led to significantly lower expression levels of key glycolytic
enzymes, such as HK2, PKM1/2, GLUT1, and
pyruvate dehydrogenase (PDH). In addition, we found that the combination of SMI and
cisplatin could inhibit cell proliferation and promote apoptosis by reducing the expression levels of p-Akt, p-mTOR, and c-Myc, and then, it reduced the glycolysis level. These results suggest that SMI enhances the antitumor effect of
cisplatin via
glucose metabolism reprogramming. Therefore, the combination of SMI and
cisplatin may be a potential therapeutic strategy to treat
cisplatin-resistant
nonsmall cell lung cancer.