Bazedoxifene Inhibits Cell Viability, Colony-Forming Activity, and Cell Migration in Human Non-Small Cell Lung Cancer Cells and Improves the Treatment Efficacy of Paclitaxel and Gemcitabine

Overview

Journal Clin Respir J

Specialty Pulmonary Medicine

Date 2024 Aug 17

PMID 39152779

Authors

Yaochen Huang

Jiayuh Lin

Xiangning Fu

Lequn Li

Shenging Fu

Affiliations

Soon will be listed here.

Abstract

Background: Bazedoxifene is a third-generation selective estrogen receptor modulator that inhibits the IL6/IL6R/GP130 signaling pathway by inhibiting IL6-induced homodimerization of GP130. Considering that the IL6/IL6R/GP130 signaling pathway is important in tumorigenesis and metastasis, bazedoxifene is thought to have an antitumor effect, which has been proven preliminarily in breast cancer and pancreatic cancer but has not yet been studied in non-small cell lung cancer (NSCLC). This study is aimed at evaluating the antitumor effect of bazedoxifene in NSCLC.

Methods: A549 and H1299 NSCLC cell lines were employed and exposed to various concentrations of bazedoxifene, paclitaxel, gemcitabine, and their combinations for cell viability, colony formation, and wound healing assays to demonstrate the antitumor effect of bazedoxifene with or without paclitaxel or gemcitabine.

Results: MTT cell viability, colony formation, and wound healing assays showed that bazedoxifene was capable of inhibiting cell viability, colony formation, and cell migration in a dose-dependent manner. In addition, bazedoxifene was capable of working with paclitaxel or gemcitabine synergistically to inhibit cell viability, colony formation, and cell migration.

Conclusion: This study demonstrated the potential antitumor effect of bazedoxifene and its ability to improve the treatment efficacy of paclitaxel and gemcitabine.

References

Fu S, Lin J . Blocking Interleukin-6 and Interleukin-8 Signaling Inhibits Cell Viability, Colony-forming Activity, and Cell Migration in Human Triple-negative Breast Cancer and Pancreatic Cancer Cells. Anticancer Res. 2018; 38(11):6271-6279. DOI: 10.21873/anticanres.12983. View

Sung H, Ferlay J, Siegel R, Laversanne M, Soerjomataram I, Jemal A . Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249. DOI: 10.3322/caac.21660. View

Ge X, Peng X, Li M, Ji F, Chen J, Zhang D . OGT regulated O-GlcNacylation promotes migration and invasion by activating IL-6/STAT3 signaling in NSCLC cells. Pathol Res Pract. 2021; 225:153580. DOI: 10.1016/j.prp.2021.153580. View

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T . Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012; 9(7):676-82. PMC: 3855844. DOI: 10.1038/nmeth.2019. View

Ohe Y, Ohashi Y, Kubota K, Tamura T, Nakagawa K, Negoro S . Randomized phase III study of cisplatin plus irinotecan versus carboplatin plus paclitaxel, cisplatin plus gemcitabine, and cisplatin plus vinorelbine for advanced non-small-cell lung cancer: Four-Arm Cooperative Study in Japan. Ann Oncol. 2006; 18(2):317-23. DOI: 10.1093/annonc/mdl377. View

de Villiers T, Chines A, Palacios S, Lips P, Sawicki A, Levine A . Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: results of a 5-year, randomized, placebo-controlled phase 3 trial. Osteoporos Int. 2010; 22(2):567-76. DOI: 10.1007/s00198-010-1302-6. View

Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K . IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science. 1993; 260(5115):1808-10. DOI: 10.1126/science.8511589. View

Xia C, Dong X, Li H, Cao M, Sun D, He S . Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J (Engl). 2022; 135(5):584-590. PMC: 8920425. DOI: 10.1097/CM9.0000000000002108. View

Ettinger D, Wood D, Aisner D, Akerley W, Bauman J, Chirieac L . Non-Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017; 15(4):504-535. DOI: 10.6004/jnccn.2017.0050. View

10.

Liu Y, Gao Y, Lin T . Expression of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) in non-small cell lung cancer and its relationship with the occurrence and prognosis of cancer pain. Ann Palliat Med. 2022; 10(12):12759-12766. DOI: 10.21037/apm-21-3471. View

11.

Lee H, Zhuang G, Cao Y, Du P, Kim H, Settleman J . Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells. Cancer Cell. 2014; 26(2):207-21. DOI: 10.1016/j.ccr.2014.05.019. View

12.

Fu S, Chen X, Lo H, Lin J . Combined bazedoxifene and paclitaxel treatments inhibit cell viability, cell migration, colony formation, and tumor growth and induce apoptosis in breast cancer. Cancer Lett. 2019; 448:11-19. DOI: 10.1016/j.canlet.2019.01.026. View

13.

Hong D, Kurzrock R, Kim Y, Woessner R, Younes A, Nemunaitis J . AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer. Sci Transl Med. 2015; 7(314):314ra185. PMC: 5279222. DOI: 10.1126/scitranslmed.aac5272. View

14.

Yu Z, Tang H, Chen S, Xie Y, Shi L, Xia S . Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy. Drug Resist Updat. 2023; 67:100915. DOI: 10.1016/j.drup.2022.100915. View

15.

Mukohara T, Kudoh S, Yamauchi S, Kimura T, Yoshimura N, Kanazawa H . Expression of epidermal growth factor receptor (EGFR) and downstream-activated peptides in surgically excised non-small-cell lung cancer (NSCLC). Lung Cancer. 2003; 41(2):123-30. DOI: 10.1016/s0169-5002(03)00225-3. View

16.

Zou J, Wang L, Tang H, Liu X, Peng F, Peng C . Ferroptosis in Non-Small Cell Lung Cancer: Progression and Therapeutic Potential on It. Int J Mol Sci. 2021; 22(24). PMC: 8704137. DOI: 10.3390/ijms222413335. View

17.

Ettinger D, Wood D, Aisner D, Akerley W, Bauman J, Bharat A . NCCN Guidelines Insights: Non-Small Cell Lung Cancer, Version 2.2021. J Natl Compr Canc Netw. 2021; 19(3):254-266. DOI: 10.6004/jnccn.2021.0013. View

18.

Postmus P, Kerr K, Oudkerk M, Senan S, Waller D, Vansteenkiste J . Early and locally advanced non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017; 28(suppl_4):iv1-iv21. DOI: 10.1093/annonc/mdx222. View

19.

Chang Q, Daly L, Bromberg J . The IL-6 feed-forward loop: a driver of tumorigenesis. Semin Immunol. 2014; 26(1):48-53. DOI: 10.1016/j.smim.2014.01.007. View

20.

Yavropoulou M, Makras P, Anastasilakis A . Bazedoxifene for the treatment of osteoporosis. Expert Opin Pharmacother. 2019; 20(10):1201-1210. DOI: 10.1080/14656566.2019.1615882. View