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Effect and possible mechanism of Salvianolic acid B on radiosensitivity of non-small cell lung cancer
Wang Guohui1, Yang Xiongtao2, Yang Gaoshan3,4
1Department of Radiotherapy, Second Hospital of Hebei Medical University, Shijiazhuang 050051, China; 2Peking University China-Japan Friendship School of Clinical Medicine, National Clinical Research Center for Respiratory Diseases, Beijing 100029, China; 3Department of Biochemistry and Biology College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China; 4Hebei Key Laboratory of Chinese Medicine Research on Cardio-Cerebrovascular Disease, Shijiazhuang 050091, China
AbstractObjective To evaluate the effect of Salvianolic acid B on the radiosensitivity of human non-small cell lung cancer cells and investigate its possible mechanism. Methods Non-small cell lung cancer cells A549 and H1299 were cultured in vitro. The toxicity of Salvianolic acid B on non-small cell lung cancer cells was detected by MTT assay. The effect of Salvianolic acid B on the radiosensitivity was assessed by clone formation assay. Transwell chamber assay was used to evaluate the effect of Salvianolic acid B on the migration of tumor cells. Western blot was employed to detect the expression levels of OTUD7B, MMP-2, MMP-9, E-cadherin, Akt and p-Akt regulated by Salvianolic acid B. Results Salvianolic acid B (5 μmol/L) could inhibit the proliferation of A549 and H1299 cells. Clone formation assay showed that Salvianolic acid B increased the radiosensitivity of A549 and H1299 cells, with a radiosensitization ratio of 1.45 and 1.38, respectively. Transwell chamber assay indicated that the ability of cell migration was significantly inhibited by Salvianolic acid B (P<0.05). Western blot revealed that the expression levels of OTUD7B in A549 and H1299 cells were induced by irradiation in a time-dependent manner. Salvianolic acid B could down-regulate the expression levels of MMP-2, MMP-9 and p-Akt, whereas up-regulate the expression level of E-cadherin by down-regulating the expression level of OTUD7B. Conclusions Salvianolic acid B can enhance the radiosensitivity of A549 and H1299 cells. The possible mechanism is that Salvianolic acid B down-regulates the expression level of OTUD7B induced by irradiation and inhibits the epithelial-mesenchymal transition process of tumor cells.
Fund:Natural Science Foundation of Hebei Province (H2021423069);Science and Technology Research Project of Higher Education Institutions of Hebei Province (BJ2021031);Doctoral Research Fund Project of Hebei University of Chinese Medicine (BSZ2021003)
Corresponding Authors:
Yang Gaoshan, Email:ygsyynzwt_007@126.com
Cite this article:
Wang Guohui,Yang Xiongtao,Yang Gaoshan. Effect and possible mechanism of Salvianolic acid B on radiosensitivity of non-small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2021, 30(12): 1304-1308.
Wang Guohui,Yang Xiongtao,Yang Gaoshan. Effect and possible mechanism of Salvianolic acid B on radiosensitivity of non-small cell lung cancer[J]. Chinese Journal of Radiation Oncology, 2021, 30(12): 1304-1308.
[1] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6):394-424. DOI:10.3322/caac.21492. [2] Molina JR, Yang P, Cassivi SD, et al. Non-small cell lung cancer:epidemiology, risk factors, treatment, and survivorship[J]. Mayo Clin Proc, 2008, 83(5):584-594. DOI:10.4065/83.5.584. [3] Cao W, Guo XW, Zheng HZ, et al. Current progress of research on pharmacologic actions of salvianolic acid B[J]. Chin J Integr Med, 2012, 18(4):316-320. DOI:10.1007/s11655-012-1052-8. [4] Katary MA, Abdelsayed R, Alhashim A, et al. Salvianolic acid B slows the progression of breast cancer cell growth via enhancement of apoptosis and reduction of oxidative stress, inflammation, and angiogenesis[J]. Int J Mol Sci, 2019, 20(22):5653. DOI:10.3390/ijms20225653. [5] Yang Y, Ge PJ, Jiang L, et al. Modulation of growth and angiogenic potential of oral squamous carcinoma cells in vitro using salvianolic acid B[J]. BMC Complement Altern Med, 2011, 11(1):54-60. DOI:10.1186/1472-6882-11-54. [6] Sha W, Zhou Y, Ling ZQ, et al. Antitumor properties of Salvianolic acid B against triple-negative and hormone receptor-positive breast cancer cells via ceramide-mediated apoptosis[J]. Oncotarget, 2018, 9(91):36331-36343. DOI:10.18632/oncotarget.26348. [7] Zhang B, Wang H, Yang L, et al. OTUD7B and NIK expression in non-small cell lung cancer:association with clinicopathological features and prognostic implications[J]. Pathol Res Pract, 2016, 212(10):893-898. DOI:10.1016/j.prp.2016.07.011. [8] Chen W, Wang N, Li RC, et al. Salvianolic acid B renders glioma cells more sensitive to radiation via Fis-1-mediated mitochondrial dysfunction[J]. Biomed Pharmacother, 2018, 107:1230-1236. DOI:10.1016/j.biopha.2018.08.113. [9] 向元俤,刘卫红,吴娟,等. 丹酚酸B对人鼻咽癌裸鼠移植瘤模型的放疗增敏效应[J]. 华中科技大学学报(医学版),2016, 45(5):535-538,550. DOI:10.3870/j.issn.1672-0741.2016.05.012. Xiang YD. Liu WH, Wu J, et al. Radiotherapy sensitization effect of B danphenate in human nude mouse graft model of nasopharyngeal carcinoma[J]. J Huazhong Univ Sci Technol (Med Ed), 2016, 45(5):535-538,550. DOI:10.3870/j.issn.1672-0741.2016.05.012. [10] Wang B, Jie Z, Joo D, et al. TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2 signalling[J]. Nature, 2017, 545(7654):365-369. DOI:10.1038/nature22344. [11] Pang Z, Cui L, Ding N, et al. Expressions of insulin-like growth factor receptor-1 and cezanne-1 in lung adenocarcinoma[J]. Med Oncol, 2017, 34(5):78. DOI:10.1007/s12032-017-0934-1. [12] Zhao Y, Tao L, Yi J, et al. The Role of Canonical Wnt Signaling in Regulating Radioresistance[J]. Cell Physiol Biochem, 2018, 48(2):419-432. DOI:10.1159/000491774. [13] Chen W, Ren X, Wu J, et al. HSP27 associates with epithelial-mesenchymal transition, stemness and radioresistance of salivary adenoid cystic carcinoma[J]. J Cell Mol Med, 2018, 22(4):2283-2298. DOI:10.1111/jcmm.13510. [14] Yang GS, Zheng B, Qin Y, et al. Salvia miltiorrhiza-derived miRNAs suppress vascular remodeling through regulating OTUD7B/KLF4/NMHC ⅡA axis[J]. Theranostics, 2020, 10(17):7787-7811. DOI:10.7150/thno.46911. [15] Lin DD, Shen Y, Qiao S, et al. Upregulation of OTUD7B (cezanne) promotes tumor progression via AKT/VEGF Pathway in lung squamous carcinoma and adenocarcinoma[J]. Front Oncol, 2019, 9:862. DOI:10.3389/fonc.2019.00862. [16] Lei S, He Z, Chen T, et al. Long noncoding RNA 00976 promotes pancreatic cancer progression through OTUD7B by sponging miR-137 involving EGFR/MAPK pathway[J]. J Exp Clin Cancer Res, 2019, 38(1):470. DOI:10.1186/s13046-019-1388-4. [17] Chen L, Wu Q, Xu X, et al. Cancer/testis antigen LDHC promotes proliferation and metastasis by activating the PI3K/Akt/GSK-3β-signaling pathway and the in lung adenocarcinoma[J]. Exp Cell Res, 2021, 398(2):112414. DOI:10.1016/j.yexcr.2020.112414. [18] Karimi Roshan M, Soltani A, Soleimani A, et al. Role of AKT and mTOR signaling pathways in the induction of epithelial-mesenchymal transition (EMT) process[J]. Biochimie, 2019, 165:229-234. DOI:10.1016/j.biochi.2019.08.003.