Tanshinone IIA inhibits cell growth by suppressing SIX1‑induced aerobic glycolysis in non‑small cell lung cancer cells

Qi,Hailiang; Chen,Zhengyi; Qin,Yuhuan; Wang,Xianlei; Zhang,Zhihua; Li,Yazhai

doi:10.3892/ol.2022.13304

Tanshinone IIA inhibits cell growth by suppressing SIX1‑induced aerobic glycolysis in non‑small cell lung cancer cells

Authors:
- Hailiang Qi
- Zhengyi Chen
- Yuhuan Qin
- Xianlei Wang
- Zhihua Zhang
- Yazhai Li
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Affiliations: Department of Thoracic Surgery, Hebei Provincial Chest Hospital, Shijiazhuang, Hebei 050041, P.R. China, Department of Surgery, Hebei Provincial Gucheng County Hospital, Hengshui, Hebei 253800, P.R. China, Department of Rehabilitation and Physical Medicine, Hebei Provincial Gucheng County Hospital, Hengshui, Hebei 253800, P.R. China, Department of Tuberculosis, Hebei Provincial Chest Hospital, Shijiazhuang, Hebei 050041, P.R. China, Department of Technology and Education, Hebei Provincial Chest Hospital, Shijiazhuang, Hebei 050041, P.R. China, Department of Pharmacy, Hebei Provincial Chest Hospital, Shijiazhuang, Hebei 050041, P.R. China
Published online on: April 21, 2022 https://doi.org/10.3892/ol.2022.13304
Article Number: 184
Copyright: © Qi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Aerobic glycolysis plays a key role in cancer cell metabolism and contributes to tumorigenesis, including that of non‑small cell lung cancer (NSCLC). Tanshinone IIA (Tan IIA), an active compound of Salvia miltiorrhiza, exhibits antitumor properties. Multiple mechanisms are involved in the antitumor action of Tan IIA in lung cancer, such as inhibiting cell growth, promoting cell apoptosis and influencing cellular metabolism. However, the effects of Tan IIA on NSCLC cells and its mechanisms of action remain unclear. The present study shows Tan IIA dose‑dependently attenuated the growth of NSCLC cells and in vitro in a dose‑dependent manner. Moreover, Tan IIA markedly decreased the ATP level, glucose uptake and lactate production in the NSCLC cells in vitro. Tan IIA also inhibited tumor growth in a xenograft model in vivo. Mechanically, Tan IIA treatment decreased sine oculis homeobox homolog 1(SIX1) mRNA and protein levels, thus leading to the downregulation of pyruvate kinase isozyme M2, hexokinase 2 and lactate dehydrogenase A (LDHA) expression in A549 cells. SIX1 knockdown with small interfering‑RNA inhibited glycolysis in NSCLC cells, suggesting that SIX1 plays a role in the antitumor effect of Tan IIA on NSCLC cells. More importantly, it was demonstrated that SIX1 expression was stimulated in patients with NSCLC and was positively correlated with the LDH serum level. Finally, SIX1 low expression levels predicted the poor prognosis of patients with NSCLC. In conclusion, the present study showed that Tan IIA functioned as an anti‑glycolysis agent in NSCLC cells by downregulating SIX1 expression and inhibiting cell proliferation.

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