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Magnetic iron oxide nanoparticles carrying PTEN gene to reverse cisplatin-resistance of A549/CDDP cell lines

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Abstract

To evaluate the feasibility of using magnetic iron oxide nanoparticle as wild PTEN gene carrier for transfection in vitro to reverse cisplatin-resistance of A549/CDDP cells, A549/CDDP cells were transfected with the wild PTEN gene expression plasmid (pGFP-PTEN) by magnetic iron nanoparticle and lipo2000. The transfection efficiency was detected by fluorescence microscope and flow cytometer. The expression levels of PTEN mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry analysis. The effect of PTEN transfection on cell cycle enhances the sensitivity of A549/CDDP to cisplatin and nanoparticle-mediated transfection has a higher efficiency than that of the liposome-mediated group. The apoptosis level was up-regulated in PTEN transfection group. The magnetic iron oxide nanoparticle could be used as one of the ideal gene carriers for PTEN gene delivery in vitro. PTEN can be an effective target for reversing cisplatin-resistance in lung cancer.

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References

  1. STECK P A, PERSHOUSE M A, JASSER S A, YUNG W K, LIN H, LIGON A H, LANGFORD L A, BAUMGARD M L, HATTIER T, DAVIS T, FRYE C, HU R, SWEDLUND B, TENG D H, TAVTIGIAN S V. Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers [J]. Nat Genet, 1997, 15(4): 356–362.

    Article  Google Scholar 

  2. PLANCHON S M, WAITE K A, ENG C. The nuclear affairs of PTEN [J]. J Cell Sci, 2008, 121(Pt 3): 249–253.

    Article  Google Scholar 

  3. HO C M, LIN M C, HUANG S H, HUANG C J, LAI H C, CHIEN T Y, CHANG S F. PTEN promoter methylation and LOH of 10q22–23 locus in PTEN expression of ovarian clear cell adenocarcinomas [J]. Gynecol Oncol, 2009, 112(2): 307–313.

    Article  Google Scholar 

  4. IWANAGA K, YANG Y, RASO M G, MA L, HANNA A E, THILAGANATHAN N, MOGHADDAM S, EVANS C M, LI H, CAI W W, SATO M, MINNA J D, WU H, CREIGHTON C J, DEMAYO F J, WISTUBA I I, KURIE J M. Pten inactivation accelerates oncogenic K-ras-initiated tumorigenesis in a mouse model of lung cancer [J]. Cancer Res, 2008, 68(4): 1119–1127.

    Article  Google Scholar 

  5. LIM W T, ZHANG W H, MILLER C R, WATTERS J W, GAO F, VISWANATHAN A, GOVINDAN R, MCLEOD H L. PTEN and phosphorylated AKT expression and prognosis in early- and late-stage non-small cell lung cancer [J]. Oncol Rep, 2007, 17(4): 853–857.

    Google Scholar 

  6. HOSOYA Y, GEMMA A, SEIKE M, KURIMOTO F, UEMATSU K, HIBINO S, YOSHIMURA A, SHIBUYA M, KUDOH S. Alteration of the PTEN/MMAC1 gene locus in primary lung cancer with distant metastasis [J]. Lung Cancer, 1999, 25(2): 87–93.

    Article  Google Scholar 

  7. INAMURA K, TOGASHI Y, NOMURA K, NINOMIYA H, HIRAMATSU M, OKUI M, SATOH Y, OKUMURA S, NAKAGAWA K, TSUCHIYA E, ISHIKAWA Y. Up-regulation of PTEN at the transcriptional level is an adverse prognostic factor in female lung adenocarcinomas [J]. Lung Cancer, 2007, 57(2): 201–206.

    Article  Google Scholar 

  8. PERRONE F, LAMPIS A, ORSENIGO M, DI BARTOLOMEO M, GEVORGYAN A, LOSA M, FRATTINI M, RIVA C, ANDREOLA S, BAJETTA E, BERTARIO L, LEO E, PIEROTTI M A, PILOTTI S. PI3KCA/PTEN deregulation contributes to impaired responses to cetuximab in metastatic colorectal cancer patients [J]. Ann Oncol, 2009, 20(1): 84–90.

    Article  Google Scholar 

  9. TANAKA M, KOUL D, DAVIES M A, LIEBERT M, STECK P A, GROSSMAN H B. MMAC1/PTEN inhibits cell growth and induces chemosensitivity to doxorubicin in human bladder cancer cells [J]. Oncogene, 2000, 19(47): 5406–5412.

    Article  Google Scholar 

  10. ZHOU M, GU L, FINDLEY H W, JIANG R, WOODS W G. PTEN reverses MDM2-mediated chemotherapy resistance by interacting with p53 in acute lymphoblastic leukemia cells [J]. Cancer Res, 2003, 63(19): 6357–6362.

    Google Scholar 

  11. WENG L, BROWN J, ENG C. PTEN induces apoptosis and cell cycle arrest through phosphoinositol-3-kinase/Akt-dependent and -independent pathways [J]. Hum Mol Genet, 2001, 10(3): 237–42.

    Article  Google Scholar 

  12. XIN J, YANG-DE Z, JI-WEI W, LI-HUA Z, PU Y, XU Z, YU H, LI Y. Preparation and characterization of fluorimetric folate-coupled chitosan nano-carrier [J]. Journal of Central South University: Science and Technology, 2010, 41(1): 161–165. (in Chinese)

    Google Scholar 

  13. DATILES M J, JOHNSON E A, MCCARTY R E. Inhibition of the ATPase activity of the catalytic portion of ATP synthases by cationic amphiphiles [J]. Biochim Biophys Acta, 2008, 1777(4): 362–368.

    Article  Google Scholar 

  14. de MARTIMPREY H, VAUTHIER C, MALVY C, COUVREUR P. Polymer nanocarriers for the delivery of small fragments of nucleic acids: Oligonucleotides and siRNA [J]. Eur J Pharm Biopharm, 2009, 71(3): 490–504.

    Article  Google Scholar 

  15. WU H, CAO Y, WENG D, XING H, SONG X, ZHOU J, XU G, LU Y, WANG S, MA D. Effect of tumor suppressor gene PTEN on the resistance to cisplatin in human ovarian cancer cell lines and related mechanisms [J]. Cancer Lett, 2008, 271(2): 260–271.

    Article  Google Scholar 

  16. STEELMAN L S, NAVOLANIC P M, SOKOLOSKY M L, TAYLOR J R, LEHMANN B D, CHAPPELL W H, ABRAMS S L, WONG E W, STADELMAN K M, TERRIAN D M, LESLIE N R, MARTELLI A M, STIVALA F, LIBRA M, FRANKLIN R A, MCCUBREY J A. Suppression of PTEN function increases breast cancer chemotherapeutic drug resistance while conferring sensitivity to mTOR inhibitors [J]. Oncogene, 2008, 27(29): 4086–4095.

    Article  Google Scholar 

  17. WU H, WANG S, WENG D, XING H, SONG X, ZHU T, XIA X, WENG Y, XU G, MENG L, ZHOU J, MA D. Reversal of the malignant phenotype of ovarian cancer A2780 cells through transfection with wild-type PTEN gene [J]. Cancer Lett, 2008, 271(2): 205–214.

    Article  Google Scholar 

  18. WANG S, CHENG Z, YANG X, DENG K, CAO Y, CHEN H, PAN L. Effect of wild type PTEN gene on proliferation and invasion of multiple myeloma [J]. Int J Hematol, 2010, 92(1): 83–94.

    Article  Google Scholar 

  19. LI D M, SUN H. PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell cycle arrest in human glioblastoma cells [J]. Proc Natl Acad Sci USA, 1998, 95(26): 15406–1511.

    Article  Google Scholar 

  20. WENG L P, SMITH W M, DAHIA P L, ZIEBOLD U, GIL E, LEES J A, ENG C. PTEN suppresses breast cancer cell growth by phosphatase activity-dependent G1 arrest followed by cell death [J]. Cancer Res, 1999, 59(22): 5808–5814.

    Google Scholar 

  21. BRUNI P, BOCCIA A, BALDASSARRE G, TRAPASSO F, SANTORO M, CHIAPPETTA G, FUSCO A, VIGLIETTO G. PTEN expression is reduced in a subset of sporadic thyroid carcinomas: Evidence that PTEN-growth suppressing activity in thyroid cancer cells mediated by p27kip1 [J]. Oncogene, 2000. 19(28): 3146–3155.

    Article  Google Scholar 

  22. KNOBLOCH J, SCHMITZ I, GOTZ K, SCHULZE-OSTHOFF K, RUTHER U. Thalidomide induces limb anomalies by PTEN stabilization, Akt suppression, and stimulation of caspase-dependent cell death [J]. Mol Cell Biol, 2008, 28(2): 529–538.

    Article  Google Scholar 

  23. THOMAS M, KLIBANOV A M. Non-viral gene therapy: Polycation-mediated DNA delivery [J]. Appl Microbiol Biotechnol, 2003, 62(1): 27–34.

    Article  Google Scholar 

  24. SORSCHER S M. Metastatic acinar cell carcinoma of the pancreas responding to gemcitabine, 5-fluorouracil and leucovorin therapy: A case report [J]. Eur J Cancer Care (Engl), 2009, 18(3): 318–319.

    Article  Google Scholar 

  25. KROTZ F, de WIT C, SOHN H Y, ZAHLER S, GLOE T, POHL U, PLANK C. Magnetofection-A highly efficient tool for antisense oligonucleotide delivery in vitro and in vivo [J]. Mol Ther, 2003, 7(5): 700–710.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Geriatric Medicine, Department of Respiratory, Xiangya Hospital of Central South University, Changsha, 410008, China

    Ling-feng Min  (闵凌峰), Ling-ling He  (何玲玲), Qiong Chen  (陈琼), Qiao Yu  (俞巧) & Ming-xuan Xie  (谢明萱)

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  1. Ling-feng Min  (闵凌峰)
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  2. Ling-ling He  (何玲玲)
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  3. Qiong Chen  (陈琼)
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  4. Qiao Yu  (俞巧)
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  5. Ming-xuan Xie  (谢明萱)
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Correspondence to Qiong Chen  (陈琼).

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Foundation item: Project(07JJ3055) supported by the Natural Science Foundation of Hunan Province, China

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Min, Lf., He, Ll., Chen, Q. et al. Magnetic iron oxide nanoparticles carrying PTEN gene to reverse cisplatin-resistance of A549/CDDP cell lines. J. Cent. South Univ. Technol. 19, 331–339 (2012). https://doi.org/10.1007/s11771-012-1009-2

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  • DOI: https://doi.org/10.1007/s11771-012-1009-2

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