Salvia miltiorrhiza inhibited lung cancer through aerobic glycolysis suppression.

Lung cancer causes the most cancer deaths and needs new treatment strategies urgently. Salvia miltiorrhiza is a classical Chinese herb and a strong candidate for tumor treatment. The study found that the aqueous extract of Salvia miltiorrhiza (DSAE), ethanol extract of Salvia miltiorrhiza (DSEE), and its active components danshensu (DSS) and dihydrotanshinone I (DHI), exhibited antineoplastic effects in vivo and in vitro. Meanwhile, DSAE, DSEE, DSS, and DHI reduced glycolysis metabolites (ATP, lactate, and pyruvate contents) production, decreased aerobic glycolysis enzymes, and inhibited Seahorse indexes (OCR and ECAR) in Lewis lung cancer cells (LLC). Data suggests that aerobic glycolysis could be inhibited by Salvia miltiorrhiza and its components. The administration of DSS and DHI further reduced the level of HKII in lung cancer cell lines that had been inhibited with HK-II antagonists (2-deoxyglucose, 2-DG; 3-bromo-pyruvate, 3-BP) or knocked down with siRNA, thereby exerting an anti-lung cancer effect. Although DSS and DHI decreased the level of HKII in HKII-Knock-In lung cancer cell line, their anti-lung cancer efficacy remained limited due to the persistent overexpression of HKII in these cells. Reiterating the main points, we have discovered that the anti-lung cancer effects of Salvia miltiorrhiza may be attributed to its ability to regulate HKII expression levels, thereby inhibiting aerobic glycolysis. This study not only provides a new research paradigm for the treatment of cancer by Salvia miltiorrhiza, but also highlights the important link between glucose metabolism and the effect of Salvia Miltiorrhiza.

Depression promotes lung carcinoma progression by regulating the tumor microenvironment in tumor-bearing models of C57BL/6J mice.

Psychological stress is a common etiology among patients with lung cancer and serves as a potential indication of poor prognosis and advanced cancer clinical stage. Evidence indicates that depression is positively correlated with the evolvement of lung carcinoma. Nevertheless, the mechanisms underlying the effects of mental disorder on lung cancer have not been considerably and systemically explored. We hypothesized that mental disorder may affect the adjustment of the tumor microenvironment and immune cells. We used the chronic unpredictable mild stress (CUMS) procedure to induce depressed mice models and established tumor-bearing models of C57BL/6 J mice. Results revealed that the worsening of lung cancer was notably hastened in the CUMS + tumor group. Notably, the expression of PD-L1 in tumor issues increased in the tumor microenvironment, accompanied with a decline in the levels of CD8. On the basis of the date of tumor migration, our results indicated that MMPs and VEGF significantly increased after CUMS + tumor treatment. Thus, we demonstrated that modulation of the tumor microenvironment is pivotal for depression-promoted lung cancer migration.