Article Text

Download PDFPDF
  1. Jie Li, PhD, MD*,
  2. Geng Cui, PhD, MD,
  3. Lu Sun, MD,
  4. Shu-Juan Wang, MD*,
  5. Shuang Tian, PhD, MD*,
  6. Zheng Guan, PhD, MD*,
  7. Wen-Sheng Fan, MD*,
  8. Zhi-Feng Yan, PhD, MD*,
  9. Yi-Zhuo Yang, PhD, MD*,
  10. Yan-Qin You, MD*,
  11. Xiao-Yu Fu, MD*,
  12. Li-An Li, PhD, MD*,
  13. Ke Huang, MD*,
  14. Ya-Li Li, BD* and
  15. Yuan-Guang Meng, PhD, MD*
  1. *Departments of Gynecology and Obstetrics,
  2. Orthopedics, and
  3. Pathology, General Hospital of PLA, Beijing, People’s Republic of China.
  1. Address correspondence and reprint requests to Ya-Li Li, BD, Department of Gynecology and Obstetrics, General Hospital of PLA, No. 28, Fuxing Rd, Beijing 100853, People’s Republic of China. E-mail: yalilibeijing{at}; Yuan-Guang Meng, PhD, MD, Department of Gynecology and Obstetrics, General Hospital of PLA, No. 28, Fuxing Rd, Beijing 100853, People’s Republic of China. E-mail: yuanguang_meng{at}


Objective ARHI is a maternally imprinted tumor suppressor gene that is responsible for initiating programmed cell death and inhibiting cancer cell growth. However, the influence of ARHI on epithelial ovarian cancer cell death and the underlying mechanisms behind how ARHI regulates cancer cells still require further studies.

Methods Epithelial ovarian cancer cells TOV112D and ES-2 were used in this in vitro study. Cell proliferation, apoptosis, and autophagy activities were compared in TOV112D and ES-2 cells transfected with ARHI vectors or control vectors. Bcl-2 siRNA was transfected into TOV112D cells to investigate the roles of Bcl-2 played in regulating apoptosis and autophagy.

Results ARHI expression was reduced in TOV112D and ES-2 cells compared with normal epithelial ovarian cells (NOE095 and HOSEpiC). Overexpressed ARHI inhibited cancer cell proliferation, whereas induced forced cell apoptosis and excessive formation of autophagosomes inhibited promoted cell death. Furthermore, we found that Bcl-2 expression moderately declined in response to ARHI overexpressing in ES-2 and TOV112D cells; meanwhile, more apoptotic cells and higher LC3 level presented after silence of Bcl-2 in TOV112D cells. Reduced Bcl-2–Beclin 1 complex were observed in ARHI overexpressing cells. Moreover, modulation of ARHI to Bcl-2 expression could be ascribed partially to the activation of PI3k/AKT pathway. The addition of LY294002 enabled to suppress Bcl-2 expression and cell proliferation.

Conclusions The silence of ARHI expression in vitro seems to accelerate the malignant transformation of healthy ovarian cells by restraining apoptosis and autophagy. The overexpressed ARHI in TOV112D cancer cells suppresses the activation of PI3K/AKT and reduces the expression of Bcl-2, leading to enhanced cell apoptosis and autophagic cancer cell death.

  • ARHI
  • Bcl-2
  • Apoptosis
  • Autophagy
  • PI3K/AKT

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Jie Li, Geng Cui, and Lu Sun contributed equally to this work.

  • The authors declare no conflicts of interest.