Skip to main content
SpringerLink
Log in

Down-regulation of IGF-1R expression inhibits growth and enhances chemosensitivity of endometrial carcinoma in vitro

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The type-1 insulin-like growth factor receptor (IGF-1R) is over-expressed by endometrial carcinoma, level of IGF-1R has been correlated with tumor progression, and high IGF-1R expression has been found to be an important prognostic factor. In the study, we used lentivirus-mediated shRNA targeting IGF-1R to silence its expression, then assessed the effect of down-regulation of this receptor on cell growth and chemosensitivity to cisplatin. Lentivirus-mediate shRNA was designed and transfected to the endometrial carcinoma HEC-1B cell. The IGF-1R mRNA and related protein expression, cell proliferation ability, cell apoptosis, and cell cycle change were detected. Cell proliferation inhibition rates, cell apoptosis, and level of cleaved caspase-9 were measured in various concentrations of cisplatin. The mRNA and protein level of IGF-1R, and the phosphorylated protein p-Akt, p-Erk were all suppressed after transfection. Cell proliferation was inhibited in successive five days after transfection, the highest inhibition rate was 43.28 ± 3.55% on day 5. After transfection, 24.96 ± 1.05% cells were in G2/M phase, and cell apoptotic rate increased from 10.66 ± 0.08 to 19.92 ± 1.34%. In various concentrations of cisplatin, transfected cells proliferation was significantly inhibited which made the IC50 value drop from 21.85 uM to 10.58 uM. Incubation with different concentrations of cisplatin for 48 h, cells apoptotic rate increased to 41.92 ± 2.5, 31.13 ± 2.76, 22.21 ± 4.63%, respectively, which was accompanied with increased cleaved caspase-9 expression. Lentivirus-mediated shRNA targeting IGF-1R has the potential to develop as a clinical treatment method in advanced and chemoresistant endometrial carcinoma.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Kurman RJ, Zaino RJ, Norris HJ (1994) Endometrial carcinoma. In: Kurmann RJ (ed) Blaustein’s pathology of the female genital tract, 4th edn. Springer Verlag, New York, pp 447–448

    Google Scholar 

  2. Barakat RR, Grisby PW, Sabbatini P (2000) Corpus:epithelial tumors. In: Hoskins WJ, Perez CA, Young RC (eds) Principles and practice of gynecologic oncology, 2nd edn. Lippincott Williams and Wilkins, Philadelphia, pp 919–959

    Google Scholar 

  3. Carey MS, Gawlik C, Fung-Kee-Fung M, Chambers A, Oliver T (2006) Systematic review of systemic therapy for advanced or recurrent endometrial cancer. Gynecol Oncol 101:158–167

    Article  PubMed  CAS  Google Scholar 

  4. Werner H, Bruchim I (2009) The insulin-like growth factor-I receptor as an oncogene. Arch Physiol Biochem 115:58–71

    Article  PubMed  CAS  Google Scholar 

  5. Yavari K, Taghikhani M, Maragheh MG, Mesbah-Namin SA, Babaei MH (2009) Knockdown of IGF-IR by RNAi inhibits SW480 colon cancer cells growth in vitro. Arch Med Res 40:235–240

    Article  PubMed  CAS  Google Scholar 

  6. Sachdev D, Hartell JS, Lee AV, Zhang X, Yee D (2004) A dominant negative type I insulin-like growth factor receptor inhibits metastasis of human cancer cells. J Biol Chem 279:5017–5024

    Article  PubMed  CAS  Google Scholar 

  7. Wolf S, Lorenz J, Mossner J, Wiedmann M (2010) Treatment of biliary tract cancer with NVP- AEW541: mechanisms of action and resistance. World J Gastroenterol 16:156–166

    Article  PubMed  CAS  Google Scholar 

  8. Furukawa J, Wraight CJ, Freier SM, Peralta E, Atley LM, Monia BP, Gleav ME, Cox ME (2010) Antisense oligonucleotide targeting of insulin-like growth factor-1 receptor (IGF-1R) in prostate cancer. Prostate 70:206–218

    PubMed  CAS  Google Scholar 

  9. Yavari K, Taghikhani M, Maragheh MG, Mesbah-Namin SA, Babaei MH, Arfaee AJ, Madani H, Mi-rzaei HR (2010) SiRNA-mediated IGF-1R inhibition sensitizes human colon cancer SW480 cells to radiation. Acta Oncol 49:70–75

    Article  PubMed  CAS  Google Scholar 

  10. Wang YH, Xiong J, Wang SF, Yu Y, Wang B, Chen YX, Shi HF, Qiu Y (2010) Lentivirus mediated shRNA targeting insulin-like growth factor-1 receptor (IGF-1R) enhances chemosensitivity of osteosarcoma cells in vitro and in vivo. Mol Cell Biochem 341:225–233

    Article  PubMed  CAS  Google Scholar 

  11. Larsson O, Girnita A, Girnita L (2005) Role of insulin-like growth factor 1 receptor signalling in cancer. Br J Cancer 92:2097–2101

    Article  PubMed  CAS  Google Scholar 

  12. Ryan PD, Goss PE (2008) The emerging role of the insulin-like growth factor pathway as a therapeutic target in cancer. Oncologist 13:16–24

    Article  PubMed  CAS  Google Scholar 

  13. Pavelić J, Radaković B, Pavelić K (2007) The insulin-like growth factor-2 and its receptors (IGF-1R and IGF-2R/mannose6-phosphate) in endometrial adenocarcinoma. Gynecol Oncol 105:727–735

    Article  PubMed  Google Scholar 

  14. Kurihara S, Hakuno F, Takahashi S (2000) Insulin-like growth factor-I-dependent signal transduction pathways leading to the induction of cell growth and differentiation of human neuroblastoma cell line SH-SY5Y: the roles of MAP kinase pathway and PI3-kinase pathway. Endocr J 47:739–751

    Article  PubMed  CAS  Google Scholar 

  15. Pollak M (2008) Targeting insulin and insulin-like growth factor signalling in oncology. Curr Opin Pharmacol 8:384–392

    Article  PubMed  CAS  Google Scholar 

  16. Pollak M (2008) Insulin, insulin-like growth factors and neoplasia. Best Pract Res Clin Endocrinol Metab 22:625–638

    Article  PubMed  CAS  Google Scholar 

  17. Pfeffer S (2010) RNA silencing as a natural antiviral defense system in mammals: where are we now? Mol Ther 18:871–872

    Article  PubMed  CAS  Google Scholar 

  18. Downward J (2004) RNA interference. BMJ 328:1245–1248

    Article  PubMed  CAS  Google Scholar 

  19. Sumimoto H, Kawakami Y (2010) The RNA silencing technology applied by lentiviral vectors in oncology. Method Mol Biol 614:187–199

    Article  CAS  Google Scholar 

  20. Shu SR, Li XM, Yang YB, Zhang Y, Li T, Liang CY, Wang J (2010) Inhibitory effect of siRNA targeting IGF-1R on endometrial carcinoma. Int Immunopharmacol 11:244–249

    Article  PubMed  Google Scholar 

  21. Dong AQ, Kong MJ, Ma ZY (2007) Down-regulation of IGF-IR using small, interfering, hairpin RNA (siRNA) inhibits growth of human lung cancer cell line A549 in vitro and in nude mice. Cell Biol Int 31:500–507

    Article  PubMed  CAS  Google Scholar 

  22. LeRoith D, Helman L (2004) The new kid on the block (ade) of the IGF-1 receptor. Cancer Cell 5:201–202

    Article  PubMed  CAS  Google Scholar 

  23. Niu J, Xu Z, Li XN, Han Z (2007) siRNA-mediated type 1 insulin-like growth factor receptor silencing induces chemosensitization of a human liver cancer cell line with mutant P53. Cell Biol Int 31:156–164

    Article  PubMed  CAS  Google Scholar 

  24. Maloney EK, McLaughlin JL, Dagdigian NE, Garrett LM, Connors KM, Zhou XM, Blattler WA, Chittenden T, Singh R (2003) An anti-insulin-like growth factor I receptor antibody that is a potent inhibitor of cancer cell proliferation. Cancer Res 63:5073–5083

    PubMed  CAS  Google Scholar 

  25. Hellawell GO, Ferguson DJ, Brewster SF, Macaulay VM (2003) Chemosensitization of human prostate cancer using antisense agents targeting the type 1 insulin-like growth factor receptor. Br J Urol 91:271–277

    CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the Science and Technology Plan Project of Guang Dong Province (2007B 030502014, 00429391120223052) and the National Nature Science Foundation of China (30772332).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Sun Yat-sen University, 600 TianHe Road, Guangzhou, 510630, People’s Republic of China

    Shanrong Shu, Yuebo Yang, Xiaomao Li, Tian Li, Yu Zhang, Chengfang Xu, Changyan Liang & Xiaoyun Wang

Authors
  1. Shanrong Shu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yuebo Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaomao Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tian Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chengfang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Changyan Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiaoyun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xiaomao Li.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shu, S., Yang, Y., Li, X. et al. Down-regulation of IGF-1R expression inhibits growth and enhances chemosensitivity of endometrial carcinoma in vitro. Mol Cell Biochem 353, 225–233 (2011). https://doi.org/10.1007/s11010-011-0790-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-011-0790-9

Keywords

Search

Navigation