[Mechanism of Thymosin Beta 10 Inhibiting the Apoptosis  and Prompting Proliferation in A549 Cells]

Overview

Journal Zhongguo Fei Ai Za Zhi

Specialties Oncology
Pulmonary Medicine

Date 2014 Nov 19

PMID 25404268

Citations 3

Authors

Zixuan Li

Lianyue Qu

Hongshan Zhong

Ke Xu

Xueshan Qiu

Affiliations

Soon will be listed here.

Abstract

Background And Objective: Thymosin beta 10 (Tβ10) is one of β-thymosin family members, has a highly conserved polar 5 kDa peptides. This peptide is now regarded to be a small actin-binding protein and thereby induce depolymerization of the intracellular F-actin networks. Alteration of Tβ10 expression may alter the balance of cell growth, cell death, cell attachment and cell migration. Tβ10 also affects cell metastasis as well as proliferation, apoptosis and vascularization of cancer cells. But function of Tβ10 appear to be rather different between cancer cells, and the molecular mechanisms of β-thymosins to regulate cell apoptosis and proliferation in NSCLC (non-small cell lung cancer) cell lines are unclear. In this study, we used lung adenocarcinoma cell line A549, added Tβ10 or down-regulated the expression of Tβ10. We observed the change of apoptosis, proliferation and cell cyclin ability in A549 and the mechanisms underline them were also identified.

Methods: After A549 was treated with 100 ng/mL recombinant human Tβ10 or siTβ10, apoptosis rate of A549 and cell cycle distribution were detected by flow cytometry (FCM). CCK-8 assay was employed to determine the proliferation of A549. The mRNA level of P53, Caspase-3, Cyclin A and Cyclin E were determined by real-time PCR. The protein level of P53, Caspase-3, Cyclin A and Cyclin E were detected by Western blot.

Results: Add Tβ10 can inhibit the apoptosis and prompt the proliferation of A549. It can also increase the cell rates of S-phrase and G2/M-phrase, decrease the expression of P53 and Caspase-3, but increase the expression of Cyclin A and Cyclin E. Interferance of Tβ10 can prompt the apoptosis and inhibit the proliferation of A549. It can also increase the cell rates of G0/G1-phrase, increase the expression of P53 and Caspase-3, but decrease the expression of Cyclin A and Cyclin E.

Conclusions: In lung cancer cell line, Tβ10 can inhibit the apoptosis by increase P53, drive cells into the S and G2/M-phase, prompt cell proliferation by increase the expression of Cyclin A and Cyclin E. Tβ10 may become a potential biomarker and therapy target for non-small cell lung cancer.

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References

Dobashi Y . Cell cycle regulation and its aberrations in human lung carcinoma. Pathol Int. 2005; 55(3):95-105. DOI: 10.1111/j.1440-1827.2005.01799.x. View

Li Z, Qu L, Zhong H, Xu K, Qiu X . [Thymosin beta 10 prompted the VEGF-C expression in lung cancer cell]. Zhongguo Fei Ai Za Zhi. 2014; 17(5):378-83. PMC: 6000446. DOI: 10.3779/j.issn.1009-3419.2014.05.03. View

Varambally S, Yu J, Laxman B, Rhodes D, Mehra R, Tomlins S . Integrative genomic and proteomic analysis of prostate cancer reveals signatures of metastatic progression. Cancer Cell. 2005; 8(5):393-406. DOI: 10.1016/j.ccr.2005.10.001. View

Sribenja S, Wongkham S, Wongkham C, Yao Q, Chen C . Roles and mechanisms of β-thymosins in cell migration and cancer metastasis: an update. Cancer Invest. 2013; 31(2):103-10. DOI: 10.3109/07357907.2012.756111. View

Gu Y, Wang C, Wang Y, Qiu X, Wang E . Expression of thymosin beta10 and its role in non-small cell lung cancer. Hum Pathol. 2008; 40(1):117-24. DOI: 10.1016/j.humpath.2008.06.023. View

Othman N, Hasima Nagoor N . The role of microRNAs in the regulation of apoptosis in lung cancer and its application in cancer treatment. Biomed Res Int. 2014; 2014:318030. PMC: 4068038. DOI: 10.1155/2014/318030. View

Theunissen W, Fanni D, Nemolato S, Di Felice E, Cabras T, Gerosa C . Thymosin beta 4 and thymosin beta 10 expression in hepatocellular carcinoma. Eur J Histochem. 2014; 58(1):2242. PMC: 3980204. DOI: 10.4081/ejh.2014.2242. View

Sorenson C . Bcl-2 family members and disease. Biochim Biophys Acta. 2004; 1644(2-3):169-77. DOI: 10.1016/j.bbamcr.2003.08.010. View

Maelan A, Rasmussen T, Larsson L . Localization of thymosin beta10 in breast cancer cells: relationship to actin cytoskeletal remodeling and cell motility. Histochem Cell Biol. 2006; 127(1):109-13. DOI: 10.1007/s00418-006-0208-z. View

10.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

11.

Zhang W, Choi J, Cho Y, Oh S, Kim J, Hu L . Overexpression of the thymosin beta-10 gene in human ovarian cancer cells disrupts F-actin stress fiber and leads to apoptosis. Oncogene. 2001; 20(46):6700-6. DOI: 10.1038/sj.onc.1204683. View

12.

Kim Y, Kim B, Lee J . Thymosin β10 expression driven by the human TERT promoter induces ovarian cancer-specific apoptosis through ROS production. PLoS One. 2012; 7(5):e35399. PMC: 3356296. DOI: 10.1371/journal.pone.0035399. View

13.

Siegel R, Naishadham D, Jemal A . Cancer statistics, 2013. CA Cancer J Clin. 2013; 63(1):11-30. DOI: 10.3322/caac.21166. View

14.

Huang W, Wang B, Wang Q . Thymosin beta4 and AcSDKP inhibit the proliferation of HL-60 cells and induce their differentiation and apoptosis. Cell Biol Int. 2006; 30(6):514-20. DOI: 10.1016/j.cellbi.2006.01.009. View

15.

Sribenja S, Sawanyawisuth K, Kraiklang R, Wongkham C, Vaeteewoottacharn K, Obchoei S . Suppression of thymosin β10 increases cell migration and metastasis of cholangiocarcinoma. BMC Cancer. 2013; 13:430. PMC: 3849271. DOI: 10.1186/1471-2407-13-430. View

16.

Sribenja S, Li M, Wongkham S, Wongkham C, Yao Q, Chen C . Advances in thymosin beta10 research: differential expression, molecular mechanisms, and clinical implications in cancer and other conditions. Cancer Invest. 2009; 27(10):1016-22. DOI: 10.3109/07357900902849640. View

17.

Wang X, Harris C . p53 tumor-suppressor gene: clues to molecular carcinogenesis. J Cell Physiol. 1997; 173(2):247-55. DOI: 10.1002/(SICI)1097-4652(199711)173:2<247::AID-JCP30>3.0.CO;2-A. View

[Mechanism of Thymosin Beta 10 Inhibiting the Apoptosis and Prompting Proliferation in A549 Cells]

[Mechanism of Thymosin Beta 10 Inhibiting the Apoptosis  and Prompting Proliferation in A549 Cells]