Salvianolic Acid B Suppresses Non-Small-Cell Lung Cancer Metastasis Through PKM2-Independent Metabolic Reprogramming

Overview

Journal Evid Based Complement Alternat Med

Specialty Rehabilitation Medicine

Date 2022 May 3

PMID 35502178

Authors

Hong Zhang

Jianming Tang

Yu Cao

Tianhu Wang

Affiliations

Soon will be listed here.

Abstract

Objective: Salvianolic acid B (Sal B) has been demonstrated to be a potential chemoprevention agent for several cancers. Herein, we investigated the pharmacological function of Sal B on non-small-cell lung cancer (NSCLC) metastasis.

Methods: Two NSCLC cell lines (NCI-H2030 and NCI-H1650) were disposed of by 200 M Sal B or 10 M PKM2 agonist TEPP-46. Wound healing and transwell experiments were implemented for analyzing migratory and invasive capacities. Epithelial-to-mesenchymal transition (EMT) markers -catenin and E-cadherin were measured via western blotting. Cellular bioenergetics were evaluated with glucose uptake, lactate production, enolase activity, cellular ATP levels, as well as seahorse-based oxygen consumption rate (OCR), extracellular acidification rate (ECAR) analysis. Metabolic reprogramming markers PKM2, LDHA, and GLUT1 were detected via western blotting and immunofluorescence.

Results: The results showed that Sal B disposal weakened the migration and invasion of NCI-H2030 and NCI-H1650 cells and inactivated the EMT process according to downregulation of -catenin and upregulation of E-cadherin. Sal B-treated NSCLC cells displayed decreased glucose uptake, lactate production, enolase activity, cellular ATP levels, OCR, and ECAR, indicating a reduction in metabolic reprogramming. Additionally, Sal B downregulated the expression of PKM2, LDHA, and GLUT1. TEPP-46 may reverse the inhibitory effect of Sal B on metastasis as well as metabolic reprogramming.

Conclusion: Our findings provide evidence that Sal B enables to weaken NSCLC metastasis through PKM2-independent metabolic reprogramming, which sheds light on the promising therapeutic usage of Sal B in treating NSCLC.

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References

Zhao M, Li F, Jian Y, Wang X, Yang H, Wang J . Salvianolic acid B regulates macrophage polarization in ischemic/reperfused hearts by inhibiting mTORC1-induced glycolysis. Eur J Pharmacol. 2020; 871:172916. DOI: 10.1016/j.ejphar.2020.172916. View

Zhu X, Chen L, Liu L, Niu X . EMT-Mediated Acquired EGFR-TKI Resistance in NSCLC: Mechanisms and Strategies. Front Oncol. 2019; 9:1044. PMC: 6798878. DOI: 10.3389/fonc.2019.01044. View

Wang C, Zhang S, Liu J, Tian Y, Ma B, Xu S . Secreted Pyruvate Kinase M2 Promotes Lung Cancer Metastasis through Activating the Integrin Beta1/FAK Signaling Pathway. Cell Rep. 2020; 30(6):1780-1797.e6. DOI: 10.1016/j.celrep.2020.01.037. View

Sun Y, Niu X, Wang G, Qiao X, Chen L, Zhong M . A Novel lncRNA ENST00000512916 Facilitates Cell Proliferation, Migration and Cell Cycle Progression in Ameloblastoma. Onco Targets Ther. 2020; 13:1519-1531. PMC: 7037065. DOI: 10.2147/OTT.S236158. View

Qiao J, Liu A, Liu J, Guan D, Chen T . Salvianolic acid B (Sal B) alleviates the decreased activity induced by prednisolone acetate on osteoblasts by up-regulation of bone formation and differentiation genes. Food Funct. 2019; 10(9):6184-6192. DOI: 10.1039/c9fo01246j. View

Li L, Liu H, Du L, Xi P, Wang Q, Li Y . miR-449a Suppresses LDHA-Mediated Glycolysis to Enhance the Sensitivity of Non-Small Cell Lung Cancer Cells to Ionizing Radiation. Oncol Res. 2017; 26(4):547-556. PMC: 7844793. DOI: 10.3727/096504017X15016337254605. View

Sun H, Zhu A, Zhang L, Zhang J, Zhong Z, Wang F . Knockdown of PKM2 Suppresses Tumor Growth and Invasion in Lung Adenocarcinoma. Int J Mol Sci. 2015; 16(10):24574-87. PMC: 4632765. DOI: 10.3390/ijms161024574. View

Kim N, Kim H, Lee K, Hong Y, Cho J, Choi J . Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma. Nat Commun. 2020; 11(1):2285. PMC: 7210975. DOI: 10.1038/s41467-020-16164-1. View

Dowling C, Zhang H, Chonghaile T, Wong K . Shining a light on metabolic vulnerabilities in non-small cell lung cancer. Biochim Biophys Acta Rev Cancer. 2020; 1875(1):188462. PMC: 7836022. DOI: 10.1016/j.bbcan.2020.188462. View

10.

Katary M, Abdelsayed R, Alhashim A, Abdelhasib M, Elmarakby A . Salvianolic Acid B Slows the Progression of Breast Cancer Cell Growth via Enhancement of Apoptosis and Reduction of Oxidative Stress, Inflammation, and Angiogenesis. Int J Mol Sci. 2019; 20(22). PMC: 6888679. DOI: 10.3390/ijms20225653. View

11.

Hu Y, Mu H, Deng Z . The transcription factor TEAD4 enhances lung adenocarcinoma progression through enhancing PKM2 mediated glycolysis. Cell Biol Int. 2021; 45(10):2063-2073. DOI: 10.1002/cbin.11654. View

12.

Saw S, Ong B, Chua K, Takano A, Tan D . Revisiting neoadjuvant therapy in non-small-cell lung cancer. Lancet Oncol. 2021; 22(11):e501-e516. DOI: 10.1016/S1470-2045(21)00383-1. View

13.

Chen P, Cai L, Huffman K, Yang C, Kim J, Faubert B . Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells. Mol Cell. 2019; 76(5):838-851.e5. PMC: 6898782. DOI: 10.1016/j.molcel.2019.08.028. View

14.

Singh T, Fatehi Hassanabad M, Hassanabad A . Non-small cell lung cancer: Emerging molecular targeted and immunotherapeutic agents. Biochim Biophys Acta Rev Cancer. 2021; 1876(2):188636. DOI: 10.1016/j.bbcan.2021.188636. View

15.

Kong X, Fu M, Niu X, Jiang H . Comprehensive Analysis of the Expression, Relationship to Immune Infiltration and Prognosis of TIM-1 in Cancer. Front Oncol. 2020; 10:1086. PMC: 7498659. DOI: 10.3389/fonc.2020.01086. View

16.

Wang M, Herbst R, Boshoff C . Toward personalized treatment approaches for non-small-cell lung cancer. Nat Med. 2021; 27(8):1345-1356. DOI: 10.1038/s41591-021-01450-2. View

17.

Wang D, Zhao C, Xu F, Zhang A, Jin M, Zhang K . Cisplatin-resistant NSCLC cells induced by hypoxia transmit resistance to sensitive cells through exosomal PKM2. Theranostics. 2021; 11(6):2860-2875. PMC: 7806469. DOI: 10.7150/thno.51797. View

18.

Ren R, Du Y, Niu X, Zang R . ZFPM2-AS1 transcriptionally mediated by STAT1 regulates thyroid cancer cell growth, migration and invasion via miR-515-5p/TUSC3. J Cancer. 2021; 12(11):3393-3406. PMC: 8100800. DOI: 10.7150/jca.51437. View

19.

Liu R, Li Y, Tian L, Shi H, Wang J, Liang Y . Gankyrin drives metabolic reprogramming to promote tumorigenesis, metastasis and drug resistance through activating β-catenin/c-Myc signaling in human hepatocellular carcinoma. Cancer Lett. 2018; 443:34-46. DOI: 10.1016/j.canlet.2018.11.030. View

20.

Kozlowska E, Suwinski R, Giglok M, Swierniak A, Kimmel M . Mathematical model predicts response to chemotherapy in advanced non-resectable non-small cell lung cancer patients treated with platinum-based doublet. PLoS Comput Biol. 2020; 16(10):e1008234. PMC: 7561182. DOI: 10.1371/journal.pcbi.1008234. View