Targeted inhibition of mammalian target of rapamycin (mTOR) signaling pathway inhibits proliferation and induces apoptosis of laryngeal carcinoma cells in vitro.

Abstract

AIM AND OBJECTIVE:

Laryngeal carcinoma is one of the most aggressive cancers of the head and neck region. The survival rate of patients with laryngeal carcinoma is low due to its late metastases and resistance to chemotherapy and radiotherapy. It was reported that mTOR was involved in the growth and apoptosis of various cancer cells. The aim of this study was to detect the effects of mTOR inhibition by mTOR shRNA on the proliferation, apoptosis and invasive ability of Hep-2 human laryngeal carcinoma cells in vitro.

METHODS AND STUDY DESIGN:

mTOR shRNA was designed and transfected into Hep-2 human laryngeal carcinoma cells. Untreated cells and cells treated with control vector (non-targeted shRNA) were used as control. The proliferation and apoptosis of Hep-2 cells were detected by MTT and flow cytometry. A transwell assay was used to measure the invasive ability of Hep-2. The inhibition effects on the mTOR signaling pathway by mTOR shRNA were studied using RT-PCR and Western blot.

RESULTS:

Our results showed that the mRNA and protein expression of mTOR and Akt were high in laryngeal carcinoma cells and could be inhibited by mTOR shRNA. At the same time, low expression of PTEN mRNA and protein was observed in Hep-2 cells. The expression increased when the cells were transfected with mTOR shRNA. This showed that mTOR shRNA could inhibit the proliferation and invasive ability of Hep-2 cells. It also could induce the apoptosis of Hep-2 cells in vitro.

CONCLUSIONS:

The mTOR signaling pathway plays an important role in the development of laryngeal carcinoma. The mTOR shRNA we designed in this experiment effectively inhibited the mTOR signaling pathway. It inhibited the proliferation and invasive ability of the studied laryngeal carcinoma cells and induced their apoptosis in vitro. mTOR might therefore be a useful target in the therapy of laryngeal carcinoma.

• Authors: Rongrui Li, Riguang Wang, Raosheng Zhai, Zhen Dong
• Journal: Tumori (Tumori) 2011 Nov-Dec Vol. 97 Issue 6 Pg. 781-6 ISSN: 2038-2529 [Electronic] United States
• PMID: 22322846 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• RNA, Small Interfering
• Tetrazolium Salts
• Thiazoles
• MTOR protein, human
• TOR Serine-Threonine Kinases
• thiazolyl blue

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Carcinoma, Squamous Cell (drug therapy, metabolism, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Humans
• Laryngeal Neoplasms (drug therapy, metabolism, pathology)
• Molecular Targeted Therapy (methods)
• RNA, Small Interfering (pharmacology)
• Reverse Transcriptase Polymerase Chain Reaction
• Signal Transduction (drug effects)
• TOR Serine-Threonine Kinases (antagonists & inhibitors, genetics, metabolism, pharmacology)
• Tetrazolium Salts
• Thiazoles