Skip to main content
SpringerLink
Log in

Effect of p27 gene combined with Pientzehuang (片仔癀) on tumor growth in osteosarcoma-bearing nude mice

  • Original Article
  • Published:
Chinese Journal of Integrative Medicine Aims and scope Submit manuscript

Abstract

Objective

To observe the effect of p27 gene recombinant adenovirus combined with Chinese medicine Pientzehuang (片仔癀) on the growth of xenografted human osteosarcoma in nude mice.

Methods

Tissue transplantation was used to construct the orthotopic model of human osteosarcoma Saos-2 cell in nude mice. Thirty tumor-bearing nude mice were randomly divided into 5 groups with 6 mice in each group: blank control group (model of osteosarcoma), empty vector group (recombinant adeno-associated virus-multiple cloning site), Pientzehuang group, p27 gene group and combined treatment group (p27 gene combined with Pientzehuang). The effect of combined treatment on human osteosarcoma was analyzed through the tumor formation, tumor volume and inhibition rate of tumor growth. The expression of p27 was measured by immunohistochemical staining and Western blot.

Results

The orthotopic model of osteosarcoma in nude mice was successfully constructed. The general appearance of tumor-bearing nude mice in Pientzehuang and p27 gene groups was markedly improved compared with the blank control group; and in the combined treatment group it was signifificantly improved compared with the Pientzehuang and p27 gene groups. The tumor growth in the Pientzehuang and p27 gene groups was significantly inhibited compared with the blank control group P<0.05); while in the combined treatment group it was markedly inhibited compared with the Pientzehuang and p27 gene groups (P<0.05). The rates of tumor growth inhibition were 34.1%, 56.5% and 63.8% in the Pientzehuang, p27 gene and combined treatment groups, respectively. Meanwhile, the protein expression of p27 gene in the p27 gene group was signifificantly increased compared with the blank control group (P<0.05); and it was signifificantly increased in the combined treatment group compared with the p27 gene and Pientzehuang groups (P<0.05).

Conclusion

p27 gene introduced by adenovirus combined with Pientzehuang can inhibit the growth of human osteosarcoma cell Saos-2 in nude mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Thomas DM, Johnson SA, Sims NA, Trivett MK, Slavin JL, Rubin BP, et al. Terminal osteoblast differentiation mediated by runx2 and p27 is disrupted in osteosarcoma. J Cell Biol 2004;167:925–934.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Andrés-Pons A, Gil A, Oliver MD, Sotelo NS, Pulido R. Cytoplasmic p27Kip1 counteracts the pro-apoptotic function of the open conformation of PTEN by retention and destabilization of PTEN outside of the nucleus. Cell Signal 2012;24:577–787.

    Article  PubMed  Google Scholar 

  3. Yang DS, Gao X, Ye ZM, Tao HM, Li WX. Induction of apoptosis and accumulation of p27 (Kip1) protein by proteasome inhibitor MG132 in human osteosarcoma MG-63 cells. Chin J Orthop (Chin) 2005;25:613–617.

    Google Scholar 

  4. Oh S, Kim TK, Hwang DS, Yim J. Involvement of retinoblastoma protein in p27-induced apoptosis. Cancer Lett 2000;148:105–110.

    Article  CAS  PubMed  Google Scholar 

  5. Xie QX, Han CX, Lin FD, Meng JR. Clinical significance of p27 expression in blandder cancer. Chin J Mod Med (Chin) 2002;18:19–21.

    Google Scholar 

  6. Barnes A, Pinder SE, Bell JA, Paish EC, Wencyk PM, Robertson JF, et al. Expression of p27 kip1 in breast cancer and its prognostic significance. J Pathol 2003;201:451–459.

    Article  CAS  PubMed  Google Scholar 

  7. Zhang L, Zeng QQ, Lin JH. Inhibitory effect of human p27Kip1 gene AVV virus combining with Chinese herb Pientzehuang on human osteosarcoma transplant mice model. China J Tradit Chin Med Pharm (Chin) 2009;24:511–515.

    CAS  Google Scholar 

  8. Chen CH, Liu AX. Application of Chinese material medica in treating tumor. Henan Tradit Chin Med (Chin) 2004;24:75–76.

    Google Scholar 

  9. Fujieda S, Sunaga H, Tsuzuki H, Tanaka N, Saito H. Expression of platelet-derived endothelial cell growth factor in oral and oropharyngeal carcinoma. Clin Cancer Res 1998;4:1583–1590.

    CAS  PubMed  Google Scholar 

  10. Wang CD, Huang JG, Gao X, Li Y, Zhou SY, Yan X, et al. Fangchinoline induced G1/S arrest by modulating expression of p27, PCNA, and cyclin D in human prostate carcinoma cancer PC3 cells and tumor xenograft. Biosci Biotechnol Biochem 2010;74:488–493.

    Article  CAS  PubMed  Google Scholar 

  11. Zhang HQ, Li WJ, Yu F, Liu XL, Liu GL. Clinical significance and expression of p27, cyclinD1,CDK4-Rb in different types of thyroid tumorous tissues. Chin J Clin Oncol (Chin) 2006;33:1035–1037.

    CAS  Google Scholar 

  12. Migaldi M, Zunarelli E, Sgambato A, Leocata P, Ventura L, De Gaetani C. p27Kip1 expression and survival in NO gastric carcinoma. Pathol Res Pract 2001;197:231–236.

    Article  CAS  PubMed  Google Scholar 

  13. Kagawa Y, Yoshida K, Hirai T, Toge T. Significance of the expression of p27Kip1 in esophageal squamous cell carcinomas. Dis Esophagus 2000;13:179–184.

    Article  CAS  PubMed  Google Scholar 

  14. Hirabayashi H, Ohta M, Tanaka H, Sakaguchi M, Fujii Y, Miyoshi S, et al. Prognostic significance of p27KIP1 expression in resected non-small cell lung cancers: analysis in combination with expressions of p16INK4A, pRB, and p53. J Surg Oncol 2002;81:177–184.

    Article  PubMed  Google Scholar 

  15. Dreher T, Zentgraf H, Abel U, Kappeler A, Michel MS, Bleyl U. Reduction of PTEN and p27kip1 expression correlates with tumor grade in prostate cancer. Analysis in radical prostatectomy specimens and needle biopsies. Virchows Arch 2004;444:509–517.

    Article  PubMed  Google Scholar 

  16. Katner AL, Hoang QB, Gootam P, Jaruga E, Ma Q, Gnarra J, et al. Induction of cell cycle arrest and apoptosis in human prostatecarcinoma cell by a recombinant adenovirus expressing. Prostate 2002;53:77–87.

    Article  CAS  PubMed  Google Scholar 

  17. Shinoura N, Furitsu T, Asai A, Kirino T, Hamada H. Cotransduction of p27Kip1 strongly augments Fas ligand- and caspase-8-mediated apoptosis in U-373MG glioma cells. Anticancer Res 2001;21:3261–3268.

    CAS  PubMed  Google Scholar 

  18. Harada K, Supriatno, Kawaguchi S, Onoue T, Kawashima Y, Yoshida H, et al. High antitumor activity using intratumoral injection of plasmid DNA with mutant-type p27Kip1 gene following in vivo electroporation. Oncol Rep 2005;13:201–206.

    CAS  PubMed  Google Scholar 

  19. Sasaki T, Katayose Y, Suzuki M, Yamamoto K, Shiraso S, Mizuma M, et al. Adenovirus expressing mutant p27kip1 enhanced apoptosis against cholangiocarcinoma than adenovirus-p27kip1 wild type. Hepatogastroenterology 2004;51:68–75.

    CAS  PubMed  Google Scholar 

  20. Park KH, Seol JY, Kim TY, Yoo CG, Kim YW, Han SK, et al. An adenovirus expressing mutant p27 showed more potent antitumor effects than adenovims-p27 wild type. Cancer Res 2001;61:6163–6169.

    CAS  PubMed  Google Scholar 

  21. Fan YZ, Zhao ZM, Fu JY, Chen CQ, Sun W. Norcantharidin inhibits growth of human gallbladder carcinoma xenografted tumors in nude mice by inducing apoptosis and blocking the cell cycle in vivo. Hepatobil Pancreat Dis Int 2010;9:414–422.

    CAS  Google Scholar 

  22. Morishita D, Takami M, Yoshikawa S, Katayama R, Sato S, Kukimoto-Niino M, et al. Cell-permeable carboxyl-terminal p27 (Kip1) peptide exhibits anti-tumor activity by inhibiting Pim-1 kinase. J Biol Chem 2011;286:2681–2688.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Zhang L, Yu B, Lin JH. Apoptosis induction of traditional Chinese herb Pianzihuang in human osteosarcoma U-2OS cells. China J Orthop Trauma (Chin) 2009;22:265–268.

    CAS  Google Scholar 

  24. Lai YJ, Chen JP, You YJ. Determination of four compounds in Pientzehuang by HPLC. Chin Pharm J (Chin) 2008;43:1906–1908.

    CAS  Google Scholar 

  25. Zhao SL, Huang JM. Pharmacological action research of Pientzehuang in treating cancer. World Chin Med (Chin) 2007;2:65–67.

    Google Scholar 

  26. Zhuang Q, Hong F, Shen A, Zheng L, Zeng J, Lin W, et al. Pien Tze Huang inhibits tumor cell proliferation and promotes apoptosis via suppressing the STAT3 pathway in a colorectal cancer mouse model. Int J Oncol 2012;40:1569–1574.

    CAS  PubMed  Google Scholar 

  27. Lin JM, Wei LH, Chen YQ, Liu XX, Hong ZF, Sferra TJ, et al. Pien Tze Huang induced apoptosis in human colon cancer HT-29 cells is associated with regulation of the Bcl-2 family and activation of caspase 3. Chin J Integr Med 2011;17:685–690.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cheeloo Health Science Center of Shandong University, Jinan, 250012, China

    Shou-song Ren  (任守松)

  2. Department of Spine Surgery, Jimo City People’s Hospital, Qingdao, Shandong Province, 266200, China

    Shou-song Ren  (任守松)

  3. Department of Nephrology, the Second Xiangya Hospital, Central South University, Changsha, 410011, China

    Fang Yuan  (袁 芳), Ying-hong Liu  (刘映红), Le-tian Zhou  (周乐天) & Jun Li  (李 军)

Authors
  1. Shou-song Ren  (任守松)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fang Yuan  (袁 芳)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying-hong Liu  (刘映红)
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Le-tian Zhou  (周乐天)
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jun Li  (李 军)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ying-hong Liu  (刘映红).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ren, Ss., Yuan, F., Liu, Yh. et al. Effect of p27 gene combined with Pientzehuang (片仔癀) on tumor growth in osteosarcoma-bearing nude mice. Chin. J. Integr. Med. 21, 830–836 (2015). https://doi.org/10.1007/s11655-014-1766-x

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11655-014-1766-x

Keywords

Search

Navigation