Involvement of mTOR and survivin inhibition in tamoxifen-induced apoptosis in human hepatoblastoma cell line HepG2

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Ren-Hua GuoYong-Qian Shu

Abstract

Patients with advanced hepatocellular carcinoma (HCC) have shown to benefit from tamoxifen treatment. The mechanisms of tamoxifen effects in HCC, however, are not yet clearly understood. The PI3K/Akt/mTOR signal pathway is involved in cell proliferation, tumorigenesis, and apoptosis. Over-expression of survivin has played an important role in leading to antiapoptosis. The current study investigated changes in mTOR pathway and survivin expression in hepatocarcinoma cell line HepG2 treated with tamoxifen. We detected apoptosis of hepatocarcinoma cells by flow cytometry assay. Survivin transcription level and p70S6k was demonstrated by PCR, dual-luciferase reporter assay and western blot analysis respectively. Our results are showed as follows: tamoxifen leads to apoptosis of the cells, and reduction in survivin expression, as well as a dramatic reduction in the activated form of p70S6 kinase. Twenty micromoles tamoxifen treatment significantly depresses transcription of survivin mRNA. Treating HepG2 cells with rapamycin, a specific mTOR inhibitor, significantly reduce survivin protein level but did not affect survivin transcription, which indicated that tamoxifen and rapamycin were synergistic in regards to down-regulation of sur...Continue Reading

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Citations

Apr 15, 2014·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yongjuan GuRenhua Guo
Dec 14, 2011·The Journal of Pharmacy and Pharmacology·Jing LiuYun-Peng Liu
Nov 27, 2010·Liver International : Official Journal of the International Association for the Study of the Liver·José T StefanoVenancio A F Alves
Oct 23, 2015·International Journal of Endocrinology·Maurizio MontellaAldo Giudice
Mar 14, 2013·BioMed Research International·Yao-Tsung YehShen-Nien Wang
Dec 19, 2014·BMC Complementary and Alternative Medicine·Shahrul Hisham Zainal AriffinSahidan Senafi
Feb 6, 2020·Journal of Biomedical Science·Chun Hei Antonio CheungEuphemia Leung

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