Abstract
To study the inhibition of retinoblastoma cell viability by two commonly used autophagy inhibitors, chloroquine (CQ) and 3-methyladenine (3-MA), alone or in combination with the conventional chemotherapeutic drug vincristine (VCR), and to investigate whether the mechanisms of these drugs are related to inhibition of autophagy. On retinoblastoma cell line HXO-Rb44, VCR, CQ and 3-MA were used individually or combined. The cell viability was determined by CCK8 method, and the cellular autophagic activity was determined by Western blotting of LC3 and p62. Caspase 3 fragmentation and Akt activation was also determined by Western blotting. VCR induced cell cycle arrest and apoptosis in HXO-Rb44 cells, but only inhibited autophagy at relatively high doses. Both CQ and 3-MA were synergistic with VCR to inhibit the growth of retinoblastoma cells and the combinational use significantly reduced the dosage of each drug. The lowest effective dose of CQ and 3-MA was most efficient to add on VCR; however, such dose was not sufficient to suppress autophagy in these cells. CQ could directly induce caspase activation, while 3-MA significantly inhibited Akt phosphorylation. CQ and 3-MA were synergistic with VCR to inhibit retinoblastoma cells. Ou...Continue Reading
References
Jan 1, 1991·Archives of Toxicology·A BruininkF Riesen
Jan 1, 1995·Ophthalmic Research·T ToimelaL Salminen
Nov 1, 1996·Archives of Ophthalmology·A L MurphreeC J Gomer
Dec 30, 1998·Pharmacology & Toxicology·T ToimelaH Tähti
May 7, 2002·American Journal of Ophthalmology·David J Browning
Mar 3, 2004·Neurochemical Research·Hanna MäenpääHanna Tähti
Oct 7, 2004·Ophthalmology·Kaan GündüzPinar Ozdemir Geyik
Mar 3, 2007·Cancer Research·Line Groth-PedersenMarja Jäättelä
Aug 25, 2007·Nature Reviews. Molecular Cell Biology·M Chiara MaiuriGuido Kroemer
Feb 4, 2010·The Journal of Biological Chemistry·You-Tong WuHan-Ming Shen
Feb 10, 2010·World Journal of Pediatrics : WJP·Jiao-Yang CaiJing Chen
Jun 25, 2010·Investigative Ophthalmology & Visual Science·Young Hee YoonJae-Young Koh
May 7, 2011·Investigative Ophthalmology & Visual Science·Moutushy MitraSubramanian Krishnakumar
Oct 4, 2011·Archives of Toxicology·Amelia J McFarlandGary D Grant
Nov 24, 2011·Autophagy·ZhenZhen ZhanXu Dong Zhang
Mar 15, 2012·Lancet·Helen DimarasBrenda L Gallie
Apr 27, 2012·Nature Reviews. Cancer·Eileen White
May 1, 2012·PloS One·Heli HouQinghua Shi
Jan 1, 2011·International Journal of Ophthalmology·Jun-Jun SheZi-Ming Wang
Oct 24, 2012·PloS One·Elke FiratGabriele Niedermann
Oct 31, 2012·International Journal of Molecular Sciences·Xin SongXianqun Fan
Feb 12, 2013·Biochemical and Biophysical Research Communications·Yue ShengDe-Li Dong
Oct 23, 2013·PloS One·Priya SrideviJean Y J Wang
Nov 1, 2013·The Journal of Biological Chemistry·Min LiXiao-Ming Yin
Apr 3, 2014·Investigative Ophthalmology & Visual Science·Sang Jun ParkKyu Hyung Park
Apr 15, 2014·Acta Pharmacologica Sinica·Fang LiuShu-zhen Chen
Jun 28, 2014·International Journal of Molecular Medicine·Xiu ChengZhi-Wen Jiang