Silencing STAT3 may inhibit cell growth through regulating signaling pathway, telomerase, cell cycle, apoptosis and angiogenesis in hepatocellular carcinoma: potential uses for gene therapy.

Abstract

UNLABELLED:

The genesis and development of hepatocellular carcinoma (HCC) is related to the abnormity of signaling pathway, telomerase, cell cycle, apoptosis, angiogenesis, and others, in which STAT3 signaling pathway plays a key role. The HCC cell line HepG2 was transfected with small interfering RNA (siRNA) directed against STAT3. After 72 h, cell growth and cycle were analysed by MTT and Flow cytometry. Then, the protein was extracted and the protein expression of STAT3, Smad3, p44/42, TERT, caspase-3, XIAP, Grp-78, HSP-27, MMP-2, MMP-9, VEGF-A, cyclin A, and cyclin E was detected by Western blot. After the transfection, HCC cell growth was inhibited during the 24-72 h time period and the cell cycle was arrested in G0/G1. STAT3 protein expression was inhibited at 72 h after the transfection. Interestingly, Smad3, p-caspase-3, p-p44/42, Grp78, cyclin A, and cyclin E protein expression was increased at 72 h, while TERT, caspase-3, XIAP, MMP-2, MMP-9, and VEGF-A protein expression decreased at 72 h. However, P44/42, and HSP27 protein expression showed no change following transfection. The results demonstrated that STAT3 signaling pathway may participate in HCC genesis and development through regulating the protein expression of other signaling pathway, telomerase, apoptosis, cell cycle and angiogenesis; thereby, blockade of the Stat3 pathway represents a potential strategy for future treatment.

KEYWORDS:

STAT3, signaling pathway, telomerase, cell cycle, apoptosis, angiogenesis.

• Authors: X H Wang, B R Liu, B Qu, H Xing, S L Gao, J M Yin, X F Wang, Y Q Cheng
• Journal: Neoplasma (Neoplasma) Vol. 58 Issue 2 Pg. 158-71 ( 2011) ISSN: 0028-2685 [Print] Slovakia
• PMID: 21275467 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inducing Agents
• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• STAT3 Transcription Factor
• STAT3 protein, human
• Telomerase

Topics

• Angiogenesis Inducing Agents (analysis)
• Apoptosis
• Carcinoma, Hepatocellular (chemistry, etiology, pathology, therapy)
• Cell Cycle
• Cell Line, Tumor
• Endoplasmic Reticulum Chaperone BiP
• Flow Cytometry
• Gene Silencing
• Genetic Therapy
• Humans
• Liver Neoplasms (chemistry, etiology, pathology, therapy)
• STAT3 Transcription Factor (antagonists & inhibitors, genetics)
• Signal Transduction (physiology)
• Telomerase (analysis)