Advertisement

Journal of Biosciences

, Volume 42, Issue 1, pp 121–129 | Cite as

Breviscapine suppresses the growth of non-small cell lung cancer by enhancing microRNA-7 expression

Article

Abstract

Breviscapine (BVP) has previously been shown to inhibit the proliferation of hepatocellular carcinoma cells. However, little is known about the effects of BVP on non-small cell lung cancer (NSCLC) growth. Here, we aimed to study the effects of BVP on human NSCLC growth. We employed A549, NCL-H460 and A549 cells transfected with microRNA-7 (miR-7) mimic and inhibitor to investigate the effect of BVP on cell proliferation, apoptosis and apoptosis-associated molecules. The results showed that BVP significantly reduced the growth of A549 and NCL-H460 cells in a concentration-dependent and time-dependent manner, accompanied by a significant elevation of apoptosis. Additionally, the present study also confirmed that BVP-treated A549 cells showed increased levels of Bax and microRNA-7 (miR-7) and a decreased level of Bcl-2. The up-regulation of miR-7 enhanced the BVP sensitivity of NSCLC cells by suppressing cell proliferation and promoting cell apoptosis, while the inhibition of miR-7 reversed the anti-proliferative pro-apoptotic effects of BVP. Pre-treatment with miR-7 mimics enhanced the BVP-mediated down-regulation of Bax/Bcl-2 in NSCLC cells, while pre-treatment with the miR-7 inhibitor blocked the BVP-mediated down-regulation of Bax/Bcl. Taken together, these results confirm that BVP effectively inhibits NSCLC proliferation and that miR-7, as a novel target, is likely involved in BVP-induced growth suppression and the apoptosis of NSCLC cells.

Keywords

Bax Bcl-2 breviscapine miR-7 non-small cell lung cancer 

Notes

Acknowledgements

This work was financially supported by the project of medicine health science and technology plan of Zhejiang Province (No.2014KYB044)

Supplementary material

12038_2017_9670_MOESM1_ESM.doc (5.1 mb)
ESM 1 (DOC 5188 kb)

References

  1. Babae N, Bourajjaj M, Liu Y, Van Beijnum JR, Cerisoli F, Scaria PV, Verheul M, Van Berkel MP, et al. 2014 Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma. Oncotarget 5 6687–6700CrossRefPubMedPubMedCentralGoogle Scholar
  2. Furrukh M, Burney IA, Kumar S, Zahid KF and Al-Moundhri M 2013 Improving outcomes in advanced lung cancer: maintenance therapy in non-small-cell lung carcinoma. Sultan Qaboos Univ. Med. J. 13 3–18CrossRefPubMedPubMedCentralGoogle Scholar
  3. Hayashi H, Okamoto I, Morita S, Taguri M and Nakagawa K 2012 Postprogression survival for first-line chemotherapy of patients with advanced non-small-cell lung cancer. Ann. Oncol. 23 1537–1541CrossRefPubMedGoogle Scholar
  4. He X, Li C, Wu X and Yang G 2015 Docetaxel inhibits the proliferation of non-small-cell lung cancer cells via up-regulation of microRNA-7 expression. Int. J. Clin. Exp. Pathol. 8 9072–9080PubMedPubMedCentralGoogle Scholar
  5. Hotta K, Kiura K, Fujiwara Y, Takigawa N, Hisamoto A, Ichihara E, Tabata M and Tanimoto M 2011 Role of survival post-progression in phase III trials of systemic chemotherapy in advanced non-small-cell lung cancer: a systematic review. PLoS One 6 e26646CrossRefPubMedPubMedCentralGoogle Scholar
  6. Hou L, Chen J, Zheng Y and Wu C 2016 Critical role of miR-155/FoxO1/ROS axis in the regulation of non-small cell lung carcinomas. Tumour Biol. 37 5185–5192CrossRefPubMedGoogle Scholar
  7. Jia JH, Chen KP, Chen SX, Liu KZ, Fan TL and Chen YC 2008 Breviscapine, a traditional Chinese medicine, alleviates myocardial ischaemia reperfusion injury in diabetic rats. Acta Cardiol. 63 757–762CrossRefPubMedGoogle Scholar
  8. Li XL, Li YQ, Yan WM, Li HY, Xu H, Zheng XX, Guo DW and Tang LK 2004 A study of the cardioprotective effect of breviscapine during hypoxia of cardiomyocytes. Planta Med. 70 1039–1044CrossRefPubMedGoogle Scholar
  9. Liu Z, Jiang Z, Huang J, Huang S, Li Y, Yu S, Yu S and Liu X 2014a miR-7 inhibits glioblastoma growth by simultaneously interfering with the PI3K/ATK and Raf/MEK/ERK pathways. Int. J. Oncol. 44 1571–1580PubMedGoogle Scholar
  10. Liu Z, Liu Y, Li L, Xu Z, Bi B, Wang Y and Li JY 2014b MiR-7-5p is frequently downregulated in glioblastoma microvasculature and inhibits vascular endothelial cell proliferation by targeting RAF1. Tumour Biol. 35 10177–10184CrossRefPubMedGoogle Scholar
  11. Liu H, Wu X, Huang J, Peng J and Guo L 2015 miR-7 modulates chemoresistance of small cell lung cancer by repressing MRP1/ABCC1. Int. J. Exp. Pathol. 96 240–247CrossRefPubMedPubMedCentralGoogle Scholar
  12. Luo J, Li H and Zhang C 2015 MicroRNA-7 inhibits the malignant phenotypes of non-small cell lung cancer in vitro by targeting Pax6. Mol. Med. Rep. 12 5443–5448PubMedGoogle Scholar
  13. Ma C, Qi Y, Shao L, Liu M, Li X and Tang H 2013 Downregulation of miR-7 upregulates Cullin 5 (CUL5) to facilitate G1/S transition in human hepatocellular carcinoma cells. IUBMB Life 65 1026–1034CrossRefPubMedGoogle Scholar
  14. Ma J, Fang B, Zeng F, Pang H, Zhang J, Shi Y, Wu X, Cheng L, et al. 2014 Curcumin inhibits cell growth and invasion through up-regulation of miR-7 in pancreatic cancer cells. Toxicol. Lett. 231 82–91CrossRefPubMedGoogle Scholar
  15. McManus MT 2003 MicroRNAs and cancer. Semin. Cancer Biol. 13 253–258CrossRefPubMedGoogle Scholar
  16. Molina JR, Yang P, Cassivi SD, Schild SE and Adjei AA 2008 Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin. Proc. 83 584–594CrossRefPubMedPubMedCentralGoogle Scholar
  17. Qi XM, Wu GZ, Wu YG, Lin H, Shen JJ and Lin SY 2006 Renoprotective effect of breviscapine through suppression of renal macrophage recruitment in streptozotocin-induced diabetic rats. Nephron Exp. Nephrol. 104 e147–57CrossRefPubMedGoogle Scholar
  18. Reddy SD, Ohshiro K, Rayala SK and Kumar R 2008 MicroRNA-7, a homeobox D10 target, inhibits p21-activated kinase 1 and regulates its functions. Cancer Res. 68 8195–8200CrossRefPubMedPubMedCentralGoogle Scholar
  19. Siegel R, Naishadham D and Jemal A 2012 Cancer statistics 2012. CA Cancer J. Clin. 62 10–29CrossRefPubMedGoogle Scholar
  20. Swiercz A, Chechlinska M, Kupryjanczyk J, Dansonka-Mieszkowska A, Rembiszewska A, Goryca K, Kulinczak M, Zajdel M, et al. 2015 miR-7 expression in serous ovarian carcinomas. Anticancer Res. 35 2423–2429PubMedGoogle Scholar
  21. Wang Y, Ji M, Chen L, Wu X and Wang L 2013 Breviscapine reduces acute lung injury induced by left heart ischemic reperfusion in rats by inhibiting the expression of ICAM-1 and IL-18. Exp. Ther. Med. 6 1322–1326PubMedPubMedCentralGoogle Scholar
  22. Wang C, Li Y, Gao S, Cheng D, Zhao S and Liu E 2015a Breviscapine injection improves the therapeutic effect of western medicine on angina pectoris patients. PLoS One 10 e0129969CrossRefPubMedPubMedCentralGoogle Scholar
  23. Wang J, Ji SY, Liu SZ, Jing R and Lou WJ 2015b Cardioprotective effect of breviscapine: inhibition of apoptosis in H9c2 cardiomyocytes via the PI3K/Akt/eNOS pathway following simulated ischemia/reperfusion injury. Pharmazie 70 593–597PubMedGoogle Scholar
  24. Wang Y, Zhen Y, Wu X, Jiang Q, Li X, Chen Z, Zhang G and Dong L 2015c Vitexin protects brain against ischemia/reperfusion injury via modulating mitogen-activated protein kinase and apoptosis signaling in mice. Phytomedicine 22 379–384CrossRefPubMedGoogle Scholar
  25. Wei J, Xie G, Ge S, Qiu Y, Liu W, Lu A, Chen T, Li H, et al. 2012 Metabolic transformation of DMBA-induced carcinogenesis and inhibitory effect of salvianolic acid b and breviscapine treatment. J. Proteome Res. 11 1302–1316CrossRefPubMedGoogle Scholar
  26. Wu Y, Fan Q, Lu N, Tao L, Gao Y, Qi Q and Guo Q 2010 Breviscapine-induced apoptosis of human hepatocellular carcinoma cell line HepG2 was involved in its antitumor activity. Phytother. Res. 24 1188–1194CrossRefPubMedGoogle Scholar
  27. Wu L, Yang W, Zhang SN and Lu JB 2015 Alpinetin inhibits lung cancer progression and elevates sensitization drug-resistant lung cancer cells to cis-diammined dichloridoplatium. Drug Des. Devel. Ther. 9 6119–6127PubMedPubMedCentralGoogle Scholar
  28. Xiong S, Zheng Y, Jiang P, Liu R, Liu X, Qian J, Gu J, Chang L, et al. 2014 PA28gamma emerges as a novel functional target of tumour suppressor microRNA-7 in non-small-cell lung cancer. Br. J. Cancer 110 353–362CrossRefPubMedGoogle Scholar
  29. Yiming L, Wei H, Aihua L and Fandian Z 2008 Neuroprotective effects of breviscapine against apoptosis induced by transient focal cerebral ischaemia in rats. J. Pharm. Pharmacol. 60 349–355CrossRefPubMedGoogle Scholar
  30. Zhao JG, Men WF and Tang J 2015a MicroRNA-7 enhances cytotoxicity induced by gefitinib in non-small cell lung cancer via inhibiting the EGFR and IGF1R signalling pathways. Contemp. Oncol. 19 201–206Google Scholar
  31. Zhao W, Zhao JJ, Zhang L, Xu QF, Zhao YM, Shi XY and Xu AG 2015b Serum miR-21 level: a potential diagnostic and prognostic biomarker for non-small cell lung cancer. Int. J. Clin. Exp. Med. 8 14759–14763PubMedPubMedCentralGoogle Scholar
  32. Zhao Y, Tu MJ, Yu YF, Wang WP, Chen QX, Qiu JX, Yu AX and Yu AM 2015c Combination therapy with bioengineered miR-34a prodrug and doxorubicin synergistically suppresses osteosarcoma growth. Biochem. Pharmacol. 98 602–613CrossRefPubMedPubMedCentralGoogle Scholar
  33. Zhou X, Hu Y, Dai L, Wang Y, Zhou J, Wang W, Di W and Qiu L 2014 MicroRNA-7 inhibits tumor metastasis and reverses epithelial-mesenchymal transition through AKT/ERK1/2 inactivation by targeting EGFR in epithelial ovarian cancer. PLoS One 9 e96718CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Indian Academy of Sciences 2017

Authors and Affiliations

  1. 1.Department of Thoracic Tumor SurgeryZhejiang Cancer HospitalHangzhouChina
  2. 2.Department of AnesthesiaZhejiang Cancer HospitalHangzhouChina

Personalised recommendations